OBJECTIVE Granulin A(GRN A),a cytokinesis protein,is derived from proteolysis of progranulin.The previous study in our laboratory has shown that GRN A is able to inhibit cancer cell growth significantly.This study aim...OBJECTIVE Granulin A(GRN A),a cytokinesis protein,is derived from proteolysis of progranulin.The previous study in our laboratory has shown that GRN A is able to inhibit cancer cell growth significantly.This study aimed to investigate the effect of combination of GRN A and cisplatin on in vitro and in vivo on the growth of hepatocellular carcinoma.METHODS The in vitro and in vivo antitumor effects of combination of GRN A and Cisplatin were evaluated with MTS assay and subcuta.neous transplantation tumor model.Chou-Talalay method was used to calculate the combination index(CI).Colony formation assay and flow cytometry were used to detect the effects of GRN A on apoptosis.The expression of apoptosis-related proteins were detected by Western blot.RESULTS MTS assay showed that GRN A significantly inhibit hepatocellular carcinoma cells growth with the IC50 of 5.6 μmol·L^(-1),and GRN A combined with cisplatin synergistically inhibit hepatocellular carcinoma proliferation,with the CI<1.The colony-formation assay showed that GRN A significantly enhanced the inhibitory effects of cisplatin on cellular anchorage-independent growth.Flow cytometry showed that GRN A combined with cisplatin synergistically induced apoptosis,with the apoptotic rates of 5.87%,32.74%,35.67% and 67.15% in control,GRN A,Cisplatin,and combination of GRN A and Cisplatin groups,respectively.Western blot confirmed that the two drugs synergistically changed the expressions of proteins related to apoptosis.In vivo experiment indicated that combination of GRN A and cisplatin significantly suppressed tumor growth compared with single drug treatment groups.CONCLUSION The combination of GRN A and cisplatin resulted in synergistic antitumor effects against hepatocellular carcinoma both in vitro and in vivo.展开更多
文摘OBJECTIVE Granulin A(GRN A),a cytokinesis protein,is derived from proteolysis of progranulin.The previous study in our laboratory has shown that GRN A is able to inhibit cancer cell growth significantly.This study aimed to investigate the effect of combination of GRN A and cisplatin on in vitro and in vivo on the growth of hepatocellular carcinoma.METHODS The in vitro and in vivo antitumor effects of combination of GRN A and Cisplatin were evaluated with MTS assay and subcuta.neous transplantation tumor model.Chou-Talalay method was used to calculate the combination index(CI).Colony formation assay and flow cytometry were used to detect the effects of GRN A on apoptosis.The expression of apoptosis-related proteins were detected by Western blot.RESULTS MTS assay showed that GRN A significantly inhibit hepatocellular carcinoma cells growth with the IC50 of 5.6 μmol·L^(-1),and GRN A combined with cisplatin synergistically inhibit hepatocellular carcinoma proliferation,with the CI<1.The colony-formation assay showed that GRN A significantly enhanced the inhibitory effects of cisplatin on cellular anchorage-independent growth.Flow cytometry showed that GRN A combined with cisplatin synergistically induced apoptosis,with the apoptotic rates of 5.87%,32.74%,35.67% and 67.15% in control,GRN A,Cisplatin,and combination of GRN A and Cisplatin groups,respectively.Western blot confirmed that the two drugs synergistically changed the expressions of proteins related to apoptosis.In vivo experiment indicated that combination of GRN A and cisplatin significantly suppressed tumor growth compared with single drug treatment groups.CONCLUSION The combination of GRN A and cisplatin resulted in synergistic antitumor effects against hepatocellular carcinoma both in vitro and in vivo.
