The combination of rosuvastatin and meloxicam enhances the radiotherapy efficacy of MCF7, T-47D, and MDA-MB-231 breast cancer cell lines

Arvin Naeimi, Hamid Saeidi Saedi, Amir Mohsen Bakhtiyari, Kimia Shabani, Zahra Babajani, Mona Haddad Zahmatkesh

Abstract


Background and purpose: Radiotherapy is an essential treatment for breast cancer, but radioresistance remains a major obstacle. Studies suggest that statins and cyclooxygenase-2 (COX-2) inhibitors can enhance radiotherapy, yet few have examined their combined effects on breast cancer radiosensitivity. This study investigates the impact of meloxicam and rosuvastatin pretreatment on the radiosensitivity of MCF-7, T-47D, and MDA-MB-231 breast cancer cell lines.

Experimental approach: MCF-7, T-47D, and MDA-MB-231 cells were pretreated with varying concentrations of meloxicam, rosuvastatin, or both. Their response to radiation was evaluated using micronucleus, clonogenic, catalase, and superoxide dismutase (SOD) assays to assess chromosomal damage, cell survival, oxidative stress (via hydrogen peroxide degradation), and SOD antioxidant enzyme activity, respectively.

Findings/Results: Pretreatment with combined rosuvastatin (R) and meloxicam (M) at R2+M10 μM, R10+M50 μM, and R20+M100 μM increased genotoxicity and reduced colony formation across all irradiated cell lines compared to radiation alone. R10 μM, R10+M50 μM, and R20+M100 μM decreased catalase                   activity across irradiated cell lines compared to radiation alone, whereas R2+M10 μM decreased catalase activity significantly only in T-47D cells. Pretreatment with R10 μM, R2+M10 μM, R10+M50 μM, and R20+M100 μM reduced SOD activity in all irradiated cell lines compared to radiation alone.

Conclusion and implications: The combination of rosuvastatin and meloxicam at specific concentrations increased the radiation sensitivity of MCF-7, T-47D, and MDA-MB-231 cells. Combined pretreatment with rosuvastatin 10 μM and meloxicam 50 μM notably enhanced genotoxicity while reducing colony formation, catalase activity, and SOD activity compared to radiotherapy alone in MCF-7, T-47D, and MDA-MB-231 cell lines.

 

 


Keywords


Breast cancer; MB-231; MCF7; Radiosensitizer; Radiosensitization; Radiotherapy; T47D.

Full Text:

PDF

References


Farghadani R, Naidu R. Curcumin: modulator of key molecular signaling pathways in hormone-independent breast cancer. Cancers (Basel). 2021;13(14):3427,1-29.DOI: 10.3390/cancers13143427.

Taylor C, McGale P, Probert J, Broggio J, Charman J, Darby SC, et al. Breast cancer mortality in 500000 women with early invasive breast cancer diagnosed in England, 1993-2015: population based observational cohort study. BMJ. 2023;381,1-14.DOI: 10.1136/bmj-2022-074684.

Caplan L. Delay in breast cancer: implications for stage at diagnosis and survival. Front Public Health. 2014;2:87,1-5.DOI: 10.3389/fpubh.2014.00087.

Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10801 women in 17 randomised trials. Lancet. 2011;378(9804):1707-1716.DOI: 10.1016/S0140-6736(11)61629-2.

McGale P, Taylor C, Correa C, Cutter D, Duane F, Ewertz M, et al. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. 2014;383(9935): 2127-2135DOI: 10.1016/S0140-6736(14)60488-8.

Grantzau T, Thomsen MS, Væth M, Overgaard J. Risk of second primary lung cancer in women after radiotherapy for breast cancer. Radiother Oncol. 2014;111(3):366-373.DOI: 10.1016/j.radonc.2014.05.004.

Nair CK, Parida DK, Nomura T. Radioprotectors in radiotherapy. J Radiat Res. 2001;42(1):21-37.DOI: 10.1269/jrr.42.21.

Darfarin G, Salehi R, Alizadeh E, Nasiri Motlagh B, Akbarzadeh A, Farajollahi A. The effect of SiO2/Au core-shell nanoparticles on breast cancer cell’s radiotherapy. Artif Cells Nanomed Biotechnol. 2018;46(sup2):836-846.DOI: 10.1080/21691401.2018.1470526.

Xie J, Gong L, Zhu S, Yong Y, Gu Z, Zhao Y. Emerging strategies of nanomaterial‐mediated tumor radiosensitization. Adv Mater. 2019;31(3):1802244,1-25.DOI: 10.1002/adma.201802244.

Sjostedt S, Bezak E. Non-targeted effects of ionising radiation and radiotherapy. Australas Phys Eng Sci Med. 2010;33(3):219-231.DOI: 10.1007/s13246-010-0030-8.

Moding EJ, Kastan MB, Kirsch DG. Strategies for optimizing the response of cancer and normal tissues to radiation. Nat Rev Drug Discov. 2013;12(7):526-542.DOI: 10.1038/nrd4003.

Motallebzadeh E, Aghighi F, Vakili Z, Talaei SA, Mohseni M. Neuroprotective effects of alpha-lipoic acid on radiation-induced brainstem injury in rats. Res Pharm Sci. 2023;18(2):202-209.DOI: 10.4103/1735-5362.367798.

Hosseinimehr SJ, Fathi M, Ghasemi A, Shiadeh SNR, Pourfallah TA. Celecoxib mitigates genotoxicity induced by ionizing radiation in human blood lymphocytes. Res Pharm Sci. 2017;12(1):82-87.DOI: 10.4103/1735-5362.199051.

Salehifar E, Hosseinimehr SJ. The use of cyclooxygenase-2 inhibitors for improvement of efficacy of radiotherapy in cancers. Drug Discov Today. 2016;21(4):654-662.DOI: 10.1016/j.drudis.2016.02.019.

Huang X, Taeb S, Jahangiri S, Emmenegger U, Tran E, Bruce J, et al. miRNA-95 mediates radioresistance in tumors by targeting the sphingolipid phosphatase SGPP1. Cancer Res. 2013;73(23):6972-6986.DOI: 10.1158/0008-5472.CAN-13-1657.

Linam J, Yang LX. Recent developments in radiosensitization. Anticancer Res. 2015;35(5):2479-2485.PMID: 25964520.

Sanli T, Liu C, Rashid A, Hopmans SN, Tsiani E, Schultz C, et al. Lovastatin sensitizes lung cancer cells to ionizing radiation: modulation of molecular pathways of radioresistance and tumor suppression. J Thorac Oncol. 2011;6(3):439-450.DOI: 10.1097/JTO.0b013e3182049d8b.

Gil del Alcazar CR, Hardebeck MC, Mukherjee B, Tomimatsu N, Gao X, Yan J, et al. Inhibition of DNA double-strand break repair by the dual PI3K/mTOR inhibitor NVP-BEZ235 as a strategy for radiosensitization of glioblastoma. Clin Cancer Res. 2014;20(5):1235-1248.DOI: 10.1158/1078-0432.CCR-13-1607.

Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;30(7):1073-1081.DOI: 10.1093/carcin/bgp127.

Harris RE, Beebe-Donk J, Doss H, Doss DB. Aspirin, ibuprofen, and other nonsteroidal anti-inflammatory drugs in cancer prevention: a critical review of non-selective COX-2 blockade. Oncol Rep. 2005;13(4):559-583.PMID: 15756426.

Wong RSY. Role of nonsteroidal anti-inflammatory drugs (NSAIDs) in cancer prevention and cancer promotion. Adv Pharmacol Sci. 2019;2019:1-10DOI:10.1155/2019/3418975.

Bijnsdorp IV, van den Berg J, Kuipers GK, Wedekind LE, Slotman, Johannes BJ, Rijn V, et al. Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor meloxicam on human glioma cells. J Neurooncol. 2007;85:25-31.DOI: 10.1007/s11060-007-9385-4.

Kuipers GK, Slotman BJ, Wedekind LE, Stoter, van den Berg J, Sminia P, et al. Radiosensitization of human glioma cells by cyclooxygenase-2 (COX-2) inhibition: independent on COX-2 expression and dependent on the COX-2 inhibitor and sequence of administration. Int J Radiat Biol. 2007;83(10):677-685.DOI: 10.1080/09553000701558985.

Milas L, Mason KA, Crane CH, Liao Z, Masferrer J. Improvement of radiotherapy or chemoradiotherapy by targeting COX-2 enzyme. Oncology (Williston Park). 2003;17(5 Suppl 5):15-24.PMID: 12800601.

Koki AT, Leahy KM, Masferrer JL. Potential utility of COX-2 inhibitors in chemoprevention and chemotherapy. Expert Opin Investig Drugs. 1999;8(10):1623-1638.DOI: 10.1517/13543784.8.10.1623.

Ayakawa S, Shibamoto Y, Sugie C, Ito M, Ogino H, Tomita N, Kumaga M, et al. Antitumor effects of a cyclooxygenase-2 inhibitor, meloxicam, alone and in combination with radiation and/or 5-fluorouracil in cultured tumor cells. Mol Med Rep. 2009;2(4):621-625.DOI: 10.3892/mmr_00000147.

Grösch S, Maier TJ, Schiffmann S, Geisslinger G. Cyclooxygenase-2 (COX-2)-independent anticarcinogenic effects of selective COX-2 inhibitors. J Natl Cancer Inst. 2006;98(11):736-747.DOI: 10.1093/jnci/djj206.

Nielsen SF, Nordestgaard BG, Bojesen SE. Statin use and reduced cancer-related mortality. N Engl J Med. 2012;367(19):1792-1802.DOI: 10.1056/NEJMoa1201735.

Graaf MR, Beiderbeck AB, Egberts AC, Richel DJ, Guchelaar HJ. The risk of cancer in users of statins. J Clin Oncol. 2004;22(12):2388-2394.DOI: 10.1200/JCO.2004.02.027.

Lacerda L, Reddy JP, Liu D, Larson R, Li L, Masuda H, et al. Simvastatin radiosensitizes differentiated and stem-like breast cancer cell lines and is associated with improved local control in inflammatory breast cancer patients treated with postmastectomy radiation. Stem Cells Transl Med. 2014;3(7): 849-856.DOI: 10.5966/sctm.2013-0204.

Korte V, Gademann G, Gawish A, Ochel HJ. Modulation of radiosensitivity of DU145 prostate carcinoma cells by simvastatin. J Cancer Res Clin Oncol. 2023;149(8):4509-4514.DOI: 10.1007/s00432-022-04364-9.

Karagkounis G, DeVecchio J, Ferrandon S, Kalady MF. Simvastatin enhances radiation sensitivity of colorectal cancer cells. Surg Endosc. 2018;32(3):1533-1539.DOI: 10.1007/s00464-017-5841-1.

Bodgi L, Bou-Gharios J, Azzi J, Challita R, Feghaly C, Baalbaki K, et al. Effect of bisphosphonates and statins on the in vitro radiosensitivity of breast cancer cell lines. Pharmacol Rep. 2024;76(1):171-184.DOI: 10.1007/s43440-023-00560-7.

Xu Y, Yu H, Chen D, Yu J. The molecular mechanism by which statins overcome radiotherapy resistance in non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 2024;120(2):e81.DOI: 10.1016/j.ijrobp.2024.07.1957.

He Z, Mangala LS, Theriot CA, Rohde LH, Wu H, Zhang Y. Cell killing and radiosensitizing effects of atorvastatin in PC3 prostate cancer cells. J Radiat Res. 2012;53(2):225-233.DOI: 10.1269/jrr.11114.

Pyo H, Shin YK, Kim HS, Seong J, Suh CO, Kim GE. The enhancement of radiosensitivity by celecoxib, selective cyclooxygenase-2 inhibitor, on human cancer cells expressing differential levels of cyclooxygenase-2. J Korean Soc Ther Radiol Oncol. 2003;21(3):216-221.DOI: 10.1158/0008-5472.CAN-05-0220.

Comşa Ş, Cimpean AM, Raica M. The story of MCF-7 breast cancer cell line: 40 years of experience in research. Anticancer Res. 2015;35(6):3147-3154.PMID: 26026074.

Tasdemir N, Bossart EA, Li Z, Zhu L, Sikora MJ, Levine KM, et al. Comprehensive phenotypic characterization of human invasive lobular carcinoma cell lines in 2D and 3D cultures. Cancer Res. 2018;78(21):6209-6222.DOI: 10.1158/0008-5472.CAN-18-1416.

Soysal SD, Muenst S, Barbie T, Fleming T, Gao F, Spizzo G, et al. EpCAM expression varies significantly and is differentially associated with prognosis in the luminal B HER2+, basal-like, and HER2 intrinsic subtypes of breast cancer. Br J Cancer. 2013;108(7):1480-1487.DOI: 10.1038/bjc.2013.80.

Settacomkul R, Sangpairoj K, Phuagkhaopong S, Meemon K, Niamnont N, Sobhon P, et al. Ethanolic extract of Halymenia durvillei induced G2/M arrest and altered the levels of cell cycle regulatory proteins of MDA-MB-231 triple-negative breast cancer cells. Res Pharm Sci. 2023;18(3):279-291.DOI: 10.4103/1735-5362.371584.

Pratelli G, Carlisi D, Di Liberto D, Notaro A, Giuliano M, D'Anneo A, et al. MCL1 inhibition overcomes the aggressiveness features of triple-negative breast cancer MDA-MB-231 cells. Int J Mol Sci. 2023;24(13):11149,1-23.DOI: 10.3390/ijms241311149.

Hosseinimehr SJ, Ghasemi F, Flahatgar F, Rahmanian N, Ghasemi A, Asgarian-Omran H. Atorvastatin sensitizes breast and lung cancer cells to ionizing radiation. Iran J Pharm Res. 2020;19(2):80-88.DOI: 10.22037/ijpr.2020.15487.13126.

Banparvar M, Saedi HS, Zahmatkesh MH. Quercetin as a radiosensitizer for enhanced efficacy of radiotherapy in MCF-7 breast cancer cells. JCOMS. 2024;4(4):925-935.

Yu H, Sun SQ, Gu XB, Wang W, Gao XS. Atorvastatin prolongs the lifespan of radiation-induced reactive oxygen species in PC-3 prostate cancer cells to enhance the cell killing effect. Oncol Rep. 2017;37(4):2049-2056.DOI: 10.3892/or.2017.5447.

Chen YA, Shih HW, Lin YC, Hsu HY, Wu TF, Tsai CH, et al. Simvastatin sensitizes radioresistant prostate cancer cells by compromising DNA double-strand break repair. Front Pharmacol. 2018;9: 600,1-9.DOI: 10.3389/fphar.2018.00600.

Raju U, Nakata E, Yang P, Newman RA, Ang KK, Milas L. In vitro enhancement of tumor cell radiosensitivity by a selective inhibitor of cyclooxygenase-2 enzyme: mechanistic considerations. Int J Radiat Oncol Biol Phys. 2002;54(3):886-894.DOI: 10.1016/s0360-3016(02)03023-7.

Dittmann KH, Mayer C, Ohneseit PA, Raju U, Andratschke NH, Milas L, et al. Celecoxib induced tumor cell radiosensitization by inhibiting radiation induced nuclear EGFR transport and DNA-repair: a COX-2 independent mechanism. Int J Radiat Oncol Biol Phys. 2008;70(1):203-212.DOI: 10.1016/j.ijrobp.2007.08.065.

Han ZQ, Liao H, Shi F, et al. Inhibition of cyclooxygenase‑2 sensitizes lung cancer cells to radiation‑induced apoptosis. Oncol Lett. 2017;14(5):5959-5965.DOI: 10.3892/ol.2017.6940.

Bigdeli B, Goliaei B, Masoudi-Khoram N, Jooyan N, Nikoofar A, Rouhani M, et al. Enterolactone: a novel radiosensitizer for human breast cancer cell lines through impaired DNA repair and increased apoptosis. Toxicol Appl Pharmacol. 2016;313: 180-194.DOI: 10.1016/j.taap.2016.10.021.

Koller VJ, Auwärter V, Grummt T, Moosmann B, Mišík M, Knasmüller S. Investigation of the in vitro toxicological properties of the synthetic cannabimimetic drug CP-47,497-C8. Toxicol Appl Pharmacol. 2014;277(2):164-171.DOI: 10.1016/j.taap.2014.03.014.

Franken NA, Rodermond HM, Stap J, Haveman J, Van Bree C. Clonogenic assay of cells in vitro. Nat Protoc. 2006;1(5):2315-2319.DOI: 10.1038/nprot.2006.339.

Liu YP, Zheng CC, Huang YN, He ML, Xu WW, Li B. Molecular mechanisms of chemo‐and radiotherapy resistance and the potential implications for cancer treatment. MedComm (2020). 2021;2(3):315-340.DOI: 10.1002/mco2.55.

Liu FS. Mechanisms of chemotherapeutic drug resistance in cancer therapy-a quick review. Taiwan J Obstet Gynecol. 2009;48(3):239-244.DOI: 10.1016/S1028-4559(09)60296-5.

Sozer S, Ortac R, Lermioglu Erciyas F. An investigation of toxicity potential of nimesulide in juvenile rats. Turkish J Pharm Sci. 2011;8(2):147-158.

Pathak R, Kumar VP, Hauer-Jensen M, Ghosh SP. Enhanced survival in mice exposed to ionizing radiation by combination of gamma-tocotrienol and simvastatin. Mil Med. 2019;184(Supplement_1): 644-651.DOI:10.1093/milmed/usy408.

Petersen C, Petersen S, Milas L, Lang FF, Tofilon PJ. Enhancement of intrinsic tumor cell radiosensitivity induced by a selective cyclooxygenase-2 inhibitor. Clin Cancer Res. 2000;6(6):2513-2520.PMID: 10873107.

Rezano A, Ridhayanti F, Rangkuti AR, Gunawan T, Winarno GNA, Wijaya I. Cytotoxicity of simvastatin in human breast cancer MCF-7 and MDA-MB-231 cell lines. Asian Pac J Cancer Prev. 2021; 22(S1):33-42.DOI: 10.31557/APJCP.2021.22.S1.33.

Bytautaite M, Petrikaite V. Comparative study of lipophilic statin activity in 2D and 3D in vitro models of human breast cancer cell lines MDA-MB-231 and MCF-7. Onco Targets Ther. 2020:13201-13209.DOI: 10.2147/OTT.S283033.

Putra B, Wahyuningsih MSH, Sholikhah EN. Cytotoxic activity of simvastatin in T47D breast cancer cell lines and its effect on cyclin D1 expression and apoptosis. J Med Sci. 2017;49(2):47-55.DOI: 10.19106/JMedSci004901201701.

Campbell MJ, Esserman LJ, Zhou Y, Shoemaker M, Lobo M, Borman E, et al. Breast cancer growth prevention by statins. Cancer Res. 2006;66(17):8707-8714.DOI: 10.1158/0008-5472.CAN-05-4061.

Brown M, Hart C, Tawadros T, V Ramani, Sangar V, Lau M, et al. The differential effects of statins on the metastatic behaviour of prostate cancer. Br J Cancer. 2012;106(10):1689-1696.DOI: 10.1038/bjc.2012.138.

Ghosh-Choudhury N, Mandal CC, Ghosh-Choudhury N, Choudhury GG. Simvastatin induces derepression of PTEN expression via NFκB to inhibit breast cancer cell growth. Cell Signal. 2010;22(5):749-758.DOI: 10.1016/j.cellsig.2009.12.010.

Park YH, Jung HH, Ahn JS, Im YH. Statin induces inhibition of triple negative breast cancer (TNBC) cells via PI3K pathway. Biochem Biophys Res Commun. 2013;439(2):275-279.DOI: 10.1016/j.bbrc.2013.08.043.

Klawitter J, Shokati T, Moll V, Christians U, Klawitter J. Effects of lovastatin on breast cancer cells: a proteo-metabonomic study. Breast Cancer Res. 2010;12(2):R16,1-20.DOI: 10.1186/bcr2485.

Ahern TP, Lash TL, Damkier P, Christiansen PM, Cronin-Fenton DP. Statins and breast cancer prognosis: evidence and opportunities. Lancet Oncol. 2014;15(10):e461-e468.DOI: 10.1016/S1470-2045(14)70119-6.

Abdelrahman IY, Helwa R, Elkashef H, Hassan NH. Induction of P3NS1 myeloma cell death and cell cycle arrest by simvastatin and/or γ-radiation. Asian Pac J Cancer Prev. 2015;16(16):7103-7110.

DOI: 10.7314/APJCP.2015.16.16.7103.

Gopalan A, Yu W, Sanders BG, Kline K. Simvastatin inhibition of mevalonate pathway induces apoptosis in human breast cancer cells via activation of JNK/CHOP/DR5 signaling pathway. Cancer Lett. 2013;329(1):9-16.DOI: 10.1016/j.canlet.2012.08.031.

Kang KB, Wang TT, Woon CT, Cheah ES, Moore XL, Zhu C, et al. Enhancement of glioblastoma radioresponse by a selective COX-2 inhibitor celecoxib: inhibition of tumor angiogenesis with extensive tumor necrosis. Int J Radiat Oncol Biol Phys. 2007;67(3):888-896.DOI: 10.1016/j.ijrobp.2006.09.055.

Yusup G, Akutsu Y, Mutallip M, Qin W, Hu X, Komatsu-Akimoto A, et al. A COX-2 inhibitor enhances the antitumor effects of chemotherapy and radiotherapy for esophageal squamous cell carcinoma. Int J Oncol. 2014;44(4):1146-1152.DOI: 10.3892/ijo.2014.2300.

Réti A, Pap É, Adleff V, Jeney A, Kralovánszky J, Budai B. Enhanced 5-fluorouracil cytotoxicity in high cyclooxygenase-2 expressing colorectal cancer cells and xenografts induced by nonsteroidal anti-inflammatory drugs via downregulation of dihydropyrimidine dehydrogenase. Cancer Chemother Pharmacol. 2010;66(2):219-227.DOI: 10.1007/s00280-009-1149-8.

Wagemakers M, van der Wal GE, Cuberes R, Alvarez I, Andrés EM, Buxens J, et al. COX-2 inhibition combined with radiation reduces orthotopic glioma outgrowth by targeting the tumor vasculature. Transl Oncol. 2009;2(1):1-7.DOI: 10.1593/tlo.08160.

Raju U, Ariga H, Dittmann K, Nakata E, Ang KK, Milas L. Inhibition of DNA repair as a mechanism of enhanced radioresponse of head and neck carcinoma cells by a selective cyclooxygenase-2 inhibitor, celecoxib. Int J Radiat Oncol Biol Phys. 2005;63(2):520-528.DOI: 10.1016/j.ijrobp.2005.06.007.

Shin YK, Park JS, Kim HS, Kim GE, Suh CO, Yun YS, et al. Radiosensitivity enhancement by celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, via COX-2-dependent cell cycle regulation on human cancer cells expressing differential COX-2 levels. Cancer Res. 2005;65(20):9501-9509.DOI: 10.1158/0008-5472.CAN-05-0220.

Norouzi S, Norouzi M, Amini M, Amanzadeh A, Nabiuni M, Irian S, et al. Two COX-2 inhibitors induce apoptosis in human erythroleukemia K562 cells by modulating NF-κB and FHC pathways. Daru. 2016;24:1-9.DOI: 10.1186/s40199-015-0139-0.

Inoue T, Anai S, Onishi S, Miyake M, Tanaka N, ama AH, et al. Inhibition of COX-2 expression by topical diclofenac enhanced radiation sensitivity via enhancement of TRAIL in human prostate adenocarcinoma xenograft model. BMC Urol. 2013;13:1-9.DOI: 10.1186/1471-2490-13-1.

Ohneseit PA, Krebiehl G, Dittmann K, Kehlbach R, Rodemann HP. Inhibition of cyclooxygenase-2 activity by celecoxib does not lead to radiosensitization of human prostate cancer cells in vitro. Radiother Oncol. 2007;82(2):229-238.DOI: 10.1016/j.radonc.2006.11.018.

Crokart N, Radermacher K, Jordan BF, Baudelet C, Cron CO, Grégoire V, et al. Tumor radiosensitization by anti-inflammatory drugs: evidence for a new mechanism involving the oxygen effect. Cancer Res. 2005;65(17):7911-7916.DOI: 10.1158/0008-5472.CAN-05-1288.

Al-Waili NS, Butler GJ, Beale J, Hamilton RW, Lee BY, Lucas P. Hyperbaric oxygen and malignancies: a potential role in radiotherapy, chemotherapy, tumor surgery and phototherapy. Med Sci Monit.

;11(9):RA279-RA289.

PMID: 16127374.

Cheki M, Yahyapour R, Farhood B, Rezaeyan A, Shabeeb D, Amini P, et al. COX-2 in radiotherapy: a potential target for radioprotection and radiosensitization. Curr Mol Pharmacol. 2018;11(3):173-183.DOI: 10.2174/1874467211666180219102520.

Guruswamy S, Rao CV. Synergistic effects of lovastatin and celecoxib on caveolin-1 and its down-stream signaling molecules: implications for colon cancer prevention. Int J Oncol. 2009;35(5):1037-1043.DOI: 10.3892/ijo_00000418.

Reddy BS, Wang CX, Kong AN, Khor TO, Zheng X, Steele VE, et al. Prevention of azoxymethane-induced colon cancer by combination of low doses of atorvastatin, aspirin, and celecoxib in F 344 rats. Cancer Res. 2006;66(8):4542-4546.DOI: 10.1158/0008-5472.CAN-05-4428.

Patani N, Martin LA, Reis-Filho JS, Dowsett M. The role of caveolin-1 in human breast cancer. Breast Cancer Res Treat. 2012;131(1):1-15.DOI: 10.1007/s10549-011-1751-4.

Qian XL, Pan YH, Huang QY, Shi YB, Huang QY, Hu ZZ, et al. Caveolin-1: a multifaceted driver of breast cancer progression and its application in clinical treatment. Onco Targets Ther. 2019;12:1539-1552.DOI: 10.2147/OTT.S191317.

Han F, Zhang L, Zhou Y, Yi X. Caveolin-1 regulates cell apoptosis and invasion ability in paclitaxel-induced multidrug-resistant A549 lung cancer cells. Int J Clin Exp Pathol. 2015;8(8):8937-8947.PMCID: PMC4583867.

Mao Q, Unadkat JD. Role of the breast cancer resistance protein (BCRP/ABCG2) in drug transport-an update. AAPS J. 2015;17:65-82.DOI: 10.1208/s12248-014-9668-6.

Deng F, Sjöstedt N, Santo M, Neuvonen M, Niemi M, Kidron H. Novel inhibitors of breast cancer resistance protein (BCRP, ABCG2) among marketed drugs. Eur J Pharm Sci. 2023;181:106362,1-9.DOI: 10.1016/j.ejps.2022.106362.

Ungureanu D, Filip C, Artenie A, Artenie R. Evaluation of simvastatin antioxidant effects. Rev Med Chir Soc Med Nat Iasi. 2003;107(1):66-71.PMID:14755972

Qi XF, Kim DH, Yoon YS, Kim SK, Cai DQ, Teng YC, et al. Involvement of oxidative stress in simvastatin-induced apoptosis of murine CT26 colon carcinoma cells. Toxicol Lett. 2010;199(3):277-287.

DOI: 10.1016/j.toxlet.2010.09.010.

Grimes KR, Warren GW, Fang F, Xu Y, St Clair WH. Cyclooxygenase-2 inhibitor, nimesulide, improves radiation treatment against non-small cell lung cancer both in vitro and in vivo. Oncol Rep. 2006;16(4): 771-776.PMID: 16969492


Refbacks

  • There are currently no refbacks.


Creative Commons LicenseThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.