Mechanism of L-Ca2+/calpain signal transduction in verapamil inversing resistance of papillary thyroid carcinoma to doxorubicin / 中国病理生理杂志

ABSTRACT

[ ABSTRACT] AIM:To investigate the mechanism of L-type calcium channel ( L-Ca2+)/calpain signal transduc-tion pathway in verapamil inversing resistance of papillary thyroid carcinoma to doxorubicin .METHODS:Human papillary thyroid carcinoma TPC-1 cells were cultured for 2 d.For determining the appropriate concentrations and treatment time of verapamil and doxorubicin , a compatibility test was conducted to detect the cell viability by CCK-8 assay.The cells were divided into control group , doxorubicin group , verapamil group and doxorubicin +verapamil group .The techniques of whole-cell patch-clamp was used to record L-Ca2+currents.The protein expression levels of calpain 1 and LC3 were detec-ted by Western blot .RESULTS: Compared with control group , the density of L-Ca2+current decreased in doxorubicin group and verapamil group (P<0.05).Compared with verapamil group , the density of L-Ca2+current decreased in doxo-rubicin+verapamil group (P<0.01).Compared with control group, the expression of calpain 1 decreased in doxorubicin group and verapamil group (P<0.05).Compared with doxorubicin group , the expression of calpain 1 decreased in doxo-rubicin+verapamil group (P<0.05).Compared with control group , the expression of LC3 increased in doxorubicin group and verapamil group (P<0.05).Compared with doxorubicin group , the expression of LC3 increased in doxorubicin +ver-apamil group ( P<0.01) .CONCLUSION:The drug resistance of TPC-1 cells to doxorubicin may be related to the in-crease in autophagic activity .Verapamil further increases autophagic activity of TPC-1 cells, resulting in autophagic death and inversing the resistance of TPC-1 cells to doxorubicin .The mechanism may be involved in L-Ca2+/calpain 1 signal transduction pathway of autophagy .