RESUMO
PURPOSE: To investigate the effect of Met kinase inhibitor BMS-777607 on proliferation and apoptosis of tongue squamous cell carcinoma cell line CAL27. METHODS: The effect of BMS-777607 on proliferation of CAL27 was detected by MTT method, clone formation assay and EdU cell imaging. Morphological changes of apoptosis of CAL27 cells induced by BMS-777607 were observed by Heochst33342 staining. JC-1 staining was used to detect the changes of mitochondrial membrane potential of CAL27 cells treated with BMS-777607. Western blot was used to detect the effect of BMS-777607 on the expression of proliferation protein Akt, p-Akt and apoptosis-related proteins Bcl-2, Cleaved caspase-3, Bax and Parp in CAL27 cells. The data were analyzed using SPSS 22.0 software package. RESULTS: BMS-777607 inhibited proliferation and promoted apoptosis of CAL27 cells in a concentration-dependent mannerï¼Pï¼0.05ï¼. It also inhibited the expression of Bcl-2 and p-Akt and promoted the expression of Bax, Cleaved caspase-3 and Parp protein (Pï¼0.05). CONCLUSIONS: BMS-777607 can inhibit proliferation and promote apoptosis of CAL27 cells.
Assuntos
Carcinoma de Células Escamosas , Neoplasias da Língua , Aminopiridinas , Apoptose , Proteínas Reguladoras de Apoptose , Carcinoma de Células Escamosas/metabolismo , Caspase 3/farmacologia , Caspase 3/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas c-bcl-2/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/uso terapêutico , Piridonas , Língua , Neoplasias da Língua/tratamento farmacológico , Proteína X Associada a bcl-2/farmacologiaRESUMO
5-FU is a common first-line chemotherapeutic drug for the treatment of hepatocellular carcinoma. However the development of acquired resistance to 5-FU confines its clinical usages. Although this phenomenon has been the subject of intense investigation, the exact mechanism of acquired resistance to 5-FU remains elusive. Here, we report that over-expression of GRP78 contributes to acquired resistance to 5-FU in HCC by up-regulating the c-Src/LSF/TS axis. Moreover, we found that the resistance to 5-FU conferred by GRP78 is mediated by its ATPase domain. The ATPase domain differentially increased the expression of LSF, TS and promoted the phosphorylation of ERK and Akt. We further identified that GRP78 interacts physically with c-Src through its ATPase domain and promotes the phosphorylation of c-Src, which in turn increases the expression of LSF in the nucleus. Together, GRP78 confers the resistance to 5-FU by up-regulating the c-Src/LSF/TS axis via its ATPase domain.