Abstract

No target therapies are presently available in the treatment of small-cell lung cancer of Lung (SCLC). Therefore, there is a need to develop new therapeutic agents. The protein kinases are a family of genes that play critical roles in various signaling pathways. Some cancer cells show addiction to constitutive activation of certain signaling pathways for proliferation and survival. To identify new drug targets for SCLC, we screened a panel of small interfering RNAs (siRNAs) that target 720 genes encoding human protein kinases and related proteins using SBC5 SCLC cell. Polo-like kinase (PLK1) inhibition suppressed cell proliferation strongest among 20 significant promising total genes using different 5 SCLC cells as a varidation study). PLK1 mRNA expression was significantly higher than other pathological phenotypes among 20 celllines and the 200 clinical samples consist of three independent cohorts. The patients with high PLK1 expresssion was significantly associated with poor prognosis in SCLC patients. Furthermore we investigated the SN 38 and VP-16 had synergistic effect with PLK inhibition via dual PLK1 inhibition. Our results indicated that PLK1 inhibitor as BI 2536 and Volasertib, was a promising molecular target therapy for pharmacologic intervention in SCLC in both monotherapy and the combination therapy with SN38 and VP-16.

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