Adjuvant role of a T-type calcium channel blocker, TTA-A2, in lung cancer treatment with paclitaxel
作者机构:Department of Biomedical EngineeringIndian Institute of Technology HyderabadHyderabad 502285India Department of BiotechnologyIndian Institute of Technology HyderabadHyderabad 502285India
出 版 物:《Cancer Drug Resistance》 (癌症耐药(英文))
年 卷 期:2021年第4卷第4期
页 面:996-1007页
学科分类:1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金:This work was supported by Impacting Research Innovation and Technology(project code:5450) University Grant Commission fellowship(Ref.no.21/12/2014(ii)EU-V)
主 题:TTA-A2 paclitaxel adjuvant lung adenocarcinoma T-type calcium channel blocker
摘 要: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.