Aim:Chemoresistance is a prevalent issue in cancer treatment.Paclitaxel(PTX)is a microtubule-binding anticancer drug used in various cancer treatments.However,cancer cells often show chemoresistance against PTX with t...Aim:Chemoresistance is a prevalent issue in cancer treatment.Paclitaxel(PTX)is a microtubule-binding anticancer drug used in various cancer treatments.However,cancer cells often show chemoresistance against PTX with the help of P-glycoprotein(Pgp)-a drug efflux pump.It has also been observed that overexpressed T-type calcium channels(TTCCs)maintain calcium homeostasis in cancer cells,and calcium has a role in chemoresistance.Therefore,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 line.Methods: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 TTA-A2.Samples were treated with PTX at 10 nM concentration and TTA-A2 at 50 and 100 nM concentrations.PTX and TTA-A2 were used in the combination treatment at 10 and 100 nM concentrations,respectively.Results:Immunocytochemistry confirmed the expression of TTCC in A549 cells.Morphology assay showed altered morphology of A549 cells.The 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 cultures.With 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.Conclusion: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 PTX.Being a potent TTCC inhibitor,TTA-A2 may also enhance the anticancer effects of other anticancer drugs.展开更多
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)。
文摘Aim:Chemoresistance is a prevalent issue in cancer treatment.Paclitaxel(PTX)is a microtubule-binding anticancer drug used in various cancer treatments.However,cancer cells often show chemoresistance against PTX with the help of P-glycoprotein(Pgp)-a drug efflux pump.It has also been observed that overexpressed T-type calcium channels(TTCCs)maintain calcium homeostasis in cancer cells,and calcium has a role in chemoresistance.Therefore,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 line.Methods: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 TTA-A2.Samples were treated with PTX at 10 nM concentration and TTA-A2 at 50 and 100 nM concentrations.PTX and TTA-A2 were used in the combination treatment at 10 and 100 nM concentrations,respectively.Results:Immunocytochemistry confirmed the expression of TTCC in A549 cells.Morphology assay showed altered morphology of A549 cells.The 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 cultures.With 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.Conclusion: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 PTX.Being a potent TTCC inhibitor,TTA-A2 may also enhance the anticancer effects of other anticancer drugs.
