Mechanism of L-Ca2+/calpain signal transduction in verapamil inversing resistance of papillary thyroid carcinoma to doxorubicin

AIM: To investigate the mechanism of L-type calcium channel (L-Ca²⁺)/calpain signal transduction 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 detected 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 doxorubicin+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 doxorubicin+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+verapamil group (P<0.01).CONCLUSION: The drug resistance of TPC-1 cells to doxorubicin may be related to the increase 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.