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Adjuvant role of a T-type calcium channel blocker, tta-a2, in lung cancer treatment with paclitaxel

Cancer Drug Resistance 2021年第4期4卷 996-1007页

作者： Neema Kumari Pravin Shankar Giri Subha Narayan Rath Department of Biomedical Engineering Indian Institute of Technology HyderabadHyderabad 502285India Department of Biotechnology Indian Institute of Technology HyderabadHyderabad 502285India

Aim:Chemoresistance is a prevalent issue in cancer ***(PTX)is a microtubule-binding anticancer drug used in various cancer ***,cancer cells often show chemoresistance against PTX with the help of P-glycoprotein(Pgp)-a drug efflux *** has also been observed that overexpressed T-type calcium channels(TTCCs)maintain calcium homeostasis in cancer cells,and calcium has a role in ***,the aim of this study was to test the adjuvant role of tta-a2,a TTCC blocker,in enhancing the anticancer effect of PTX on the A549 lung adenocarcinoma cell ***:Morphology assay,calcium imaging assay,clonogenic assay,apoptosis assay,and real-time polymerase chain reaction(real-time PCR)were performed to find the adjuvant role of *** were treated with PTX at 10 nM concentration and tta-a2 at 50 and 100 nM *** and tta-a2 were used in the combination treatment at 10 and 100 nM concentrations,***:Immunocytochemistry confirmed the expression of TTCC in A549 *** assay showed altered morphology of A549 *** adjuvant role of tta-a2 was observed in the calcium imaging assay in spheroids,in the clonogenic assay in monolayers,and in the apoptosis assay in both *** real-time PCR,it was observed that,even though cells express the mRNA of Pgp,it is non-significant upon treatment with PTX and ***:tta-a2 can be used as an adjuvant to reduce chemoresistance in cancer cells as well as to enhance the anticancer effect of the standard anticancer drug *** a potent TTCC inhibitor,tta-a2 may also enhance the anticancer effects of other anticancer drugs.

关键词： tta-a2 paclitaxel adjuvant lung adenocarcinoma T-type calcium channel blocker

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