信号调整增强赛特铂和埃罗替尼联合应用的疗效

Title:Modulation of Signaling Enhances the Efficacy of the Combination of Satraplatin and Erlotinib

Volume: 15 Issue: 14

Author(s): Abolfazl Avan, Auke D. Adema, Eveline K. Hoebe, Charlotte M. Huijts, Amir Avan, Gareth J. Veal, Rob Ruijtenbeek, Katja Wosikowski and Godefridus J. Peters

Affiliation:

关键词: Akt，结肠癌，Erk，埃罗替尼，肺癌，赛特铂，信号

摘要: The active metabolite (JM118) of the oral platinum analog satraplatin (JM216) was investigated for potential synergism with erlotinib, an epidermal growth factor receptor (EGFR) inhibitor. JM118 sensitivity of 7 cancer cell lines (ovarian: 2008, A2780; colon: Lovo92, WiDr; lung: A549, SW1573; epidermoid: A431), was enhanced most pronounced when JM118 preceded erlotinib, which was associated with increased formation of DNA-platinum adducts. The combination increased G2/M phase accumulation and enhanced apoptosis. JM118 increased the phosphorylation of the cell cycle proteins CDK2 and CHK1 after 24 hr exposure. JM118/erlotinib enhanced Erk and Akt phosphorylation after 2 hr. JM118 significantly decreased the phosphorylation of PTEN, VEGFR, EPHA1, ERBB4, FGF-R, andSTAT3 by 20 (PTEN) to >90% (STAT3). Conclusion: Erlotinib enhanced the effects of JM118, even in cells with mutations in Ras. The mechanism of synergy involved a combination of effects on platinum-DNA adduct formation, cell cycle distribution and signaling.

Cite this article as:

Avan Abolfazl, D. Adema Auke, K. Hoebe Eveline, M. Huijts Charlotte, Avan Amir, J. Veal Gareth, Ruijtenbeek Rob, Wosikowski Katja and J. Peters Godefridus, Modulation of Signaling Enhances the Efficacy of the Combination of Satraplatin and Erlotinib, Current Drug Targets 2014; 15 (14) . https://dx.doi.org/10.2174/1389450115666141107110321