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目的探讨PI3K/Akt/m TOR通路新型抑制剂S1和Ras/Raf/MAPK抑制剂索拉非尼联合用于小细胞肺癌(SCLC)的抗肿瘤作用。方法通过体外增殖抑制试验、克隆形成试验、Transwell小室细胞侵袭试验和划痕试验,评价单独用药和联合用药对NCI-H446细胞的抑制作用。结果 S1作用24、48和72 h对NCI-H446细胞抑制作用的IC_50分别为92.82、23.19和1.79μmol/L,联用索拉非尼的IC_50分别为5.79、1.84和0.19μmol/L。药物作用72 h,所有联合组药物联合作用指数(CI)均小于1。克隆形成试验:0.4μmol/L S1+2μmol/L索拉非尼联合用药组抑制率为54.49%,克隆数与同剂量各单独给药组比较,差异均具有统计学意义(P<0.01);2μmol/L S1+2μmol/L索拉非尼联合用药组抑制率为72.46%,克隆数与索拉非尼2μmol/L组,比较差异具有统计学意义(P<0.01)。侵袭抑制试验:2μmol/L S1+4μmol/L索拉非尼联合用药组对NCI-H446细胞的抑制率高达76.84%,侵袭数与同等剂量单独给药组比较差异,均具有统计学意义(P<0.01)。迁移抑制试验:作用10 h,2μmol/L S1+4μmol/L索拉非尼联合用药对细胞的抑制率为95.15%,划痕距离显著大于索拉非尼4μmol/L组(P<0.01)。作用24 h,联合用药组抑制率为89.18%,划痕距离仍显著大于索拉非尼4μmol/L组(P<0.01)。结论 S1具有抗SCLC NCI-H446的作用,且与索拉非尼联合用药具有协同作用。
Objective To investigate the antitumor effect of a new inhibitor of PI3K / Akt / m TOR pathway and sorafenib combined with Ras / Raf / MAPK inhibitor Sorafenib for small cell lung cancer (SCLC). Methods Inhibition of NCI-H446 cells was evaluated by in vitro proliferation inhibition test, colony formation assay, Transwell cell invasion assay and scratch test. Results The inhibitory effects of S1 on NCI-H446 cells at 24, 48 and 72 h were 92.82, 23.19 and 1.79 μmol / L, respectively. The IC50 values of sorafenib combined with 5 and 10 were 5.79, 1.84 and 0.19 μmol / L, respectively. After 72 hours, the combined effect index (CI) of all combined groups was less than 1. Clone formation assay: The inhibition rate of the combination of 0.4μmol / L S1 + 2μmol / L and sorafenib was 54.49%, the difference was statistically significant (P <0.01). The inhibition rate of 2μmol / L S1 + 2μmol / L combined with sorafenib group was 72.46%. The difference was statistically significant (P <0.01) between the number of clones and sorafenib 2μmol / L group. Invasion inhibition test: The inhibitory rate of NCI-H446 cells treated with 2μmol / L S1 + 4μmol / L Sorafenib combination was as high as 76.84%, the invasion number was significantly different from that of the same dose alone group (P <0.01). Migration inhibition assay showed that the inhibition rate of cells treated with 2μmol / L S1 + 4μmol / L sorafenib was 95.15% at 10 h, and the scratch distance was significantly greater than that of sorafenib 4μmol / L group (P <0.01). For 24 h, the inhibition rate of combination group was 89.18%, and the scratch distance was still significantly greater than that of sorafenib 4 μmol / L group (P <0.01). Conclusion S1 has anti-SCLC NCI-H446 effect, and synergistic effect with sorafenib.