| Summary: | 碩士 === 國立交通大學 === 生物科技學系 === 103 === Small cell lung cancer (SCLC), exhibiting aggressive characteristics which differ from its counterpart non-small cell lung cancer (NSCLC), accounts for 13% of all lung cancer type worldwide. Chemotherapy coupling with radiotherapy remain the general management applied for SCLC treatment. Despite of good initial response, frequent relapse and resistance occurrence resulting in poor survival rate. With modest but no significant advance on survival for the past decades, growing attention have been paid on combining targeted therapy with effective therapeutic agents aiming for reinforcing drug response and overcoming resistance with lower toxic target drugs. In this study, we target inhibition of mitogen-activated protein kinase (MAPK)/ extracellular signal-regulated kinase (ERK) pathway with MEK inhibitor CI-1040 as a novel strategy for SCLC treatment. MAPK/ERK pathway not only plays an important role regulating multiple cellular processes which may determine sensitivities toward therapeutic drugs but also involves in pathogenesis of SCLC. With CI-1040 employment inhibiting cell proliferation in SCLC, experiment of combo treatment with etoposide and ABT-737 are carried out to investigate whether MAPK/ERK pathway takes part in cellular response. Etoposide, a wildly applied chemotherapeutic drug, and ABT-737, a BCL-2 inhibitor aiming for apoptosis induction, both mediate cytotoxic effect in SCLC cell lines. Experimental results of this research indicate that combination of CI-1040 with etoposide and ABT-737 enhance cell growth inhibition by interfering cell cycle progression and apoptosis promotion. Cross response on PI3K/AKT pathway after drug treatment is also involved in the enforcement. Therefore, MAPK/ERK pathway inhibition may be considered a way to reinforce antitumor ability mediated by therapeutic agents in SCLC treatment.
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