Synergistic antitumor activity of pro-apoptotic agent PAC-1 with cisplatinum by the activation of CASP3 in pulmonary adenocarcinoma cell line H1299
Synergistic antitumor activity of pro-apoptotic agent PAC-1 with cisplatinum by the activation of CASP3 in pulmonary adenocarcinoma cell line H1299
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DOI：
10.1111/ajco.12419
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发表时间：
2016-03-01
影响因子：
1.9
通讯作者：
Jin, Tian-en
中科院分区：
文献类型：
--
作者：
Huang, Jian-qing;Liang, Hong-ling;Jin, Tian-en
Aim: Evasion of apoptosis is a hallmark of human cancer cells. We sought to explore the potential synergistic antitumor activity and underlying mechanisms of the pro-apoptotic agent PAC-1 plus cisplatinum (Cis) in non-small cell lung cancer (NSCLC) cell lines.Methods: The adenocarcinoma cell lines H1299, A549, PC9, H1650 and H1975 were used as in vitro models. Colorimetric MTT assays, Western blotting and flow cytometry were used to evaluate the anti-growth effects of PAC-1 and/or Cis and apoptosis status. The activated form of CASP3 (C-CASP3) was assessed by immunofluorescent staining.Results: Single-agent Cis and PAC-1 were able to inhibit the cancer cell growth in certain dose ranges, with IC50 values of 1.9-11.7 and 5.6-14.8 mu M, respectively. Sequential Cis -> PAC-1 or concurrent Cis + PAC-1, but not PAC-1 -> Cis combinations showed synergistic effects on cell growth inhibition in H1299 cells (combination index, CI 1.0). Flow cytometric analysis showed that Cis -> PAC-1 sequential combination showed strong proapoptotic effects in H1299 cells. Western blots showed that in H1299, PC9 and H1975 cells, PAC-1 promoted the C-CASP3, but only in H1299 cells was there a synergistic effect with Cis on the CASP3 activation.Conclusions: PAC-1 showed anti-tumor activity in NSCLCs in vitro and a synergistic effect with cisplatin in EGFR(wt)KRAS(wt) H1299 cells. Our data suggest a potential treatment approach using cisplatin plus a pro-apoptotic agent acting via CASP3 activation for this subgroup of pulmonary adenocarcinomas.
