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Apoptosis

, Volume 21, Issue 12, pp 1398–1407 | Cite as

Oxymatrine synergistically enhances antitumor activity of oxaliplatin in colon carcinoma through PI3K/AKT/mTOR pathway

  • Yan Liu
  • Tingting Bi
  • Zheng Wang
  • Guoliang Wu
  • Liqiang Qian
  • Quangen GaoEmail author
  • Genhai Shen
Article

Abstract

Oxymatrine (OMT), one of the main active components of extracts from the dry roots of Sophora flavescens, has been reported to possess many pharmacological properties including cancer-preventive and anti-cancer effects. The aim of the present study is to explore the efficiency of combination therapy with OMT and oxaliplatin (OXA) and identify the in vitro and in vivo cytotoxicity on colon cancer lines (HT29 and SW480) and mice model. Cells were treated with OMT and/or OXA and subjected to cell viability, colony formation, apoptosis, cell cycle, western blotting, xenograft tumorigenicity assay and immunohistochemistry. The results demonstrated that OMT and OXA inhibited the proliferation of colon cancer cells, and combination therapy of OMT and OXA resulted in a combination index < 1, indicating a synergistic effect. Co-treatment with OMT and OXA caused G0/G1 phase arrest by upregulating P21, P27 and downregulating cyclin D, and induced apoptosis through decreasing the expression of p-PI3K, p-AKT, p-mTOR, p-p70S6K. In addition, pretreatment with a specific PI3K/AKT activator (IGF-1) significantly neutralized the pro-apoptotic activity of OXA + OMT, demonstrating the important role of PI3K/AKT in this process. Moreover, in nude mice model, co-treatment displayed more efficient inhibition of tumor weight and volume on SW480 xenograft mouse model than single-agent treatment with OXA or OMT. Immunohistochemistry analysis suggests the combinations greatly suppressed tumor proliferation, which consistent with our in vitro results. In conclusion, our findings highlight that the combination therapy with OMT and OXA exerted synergistic antitumor effects in colon cancer cells through PI3K/AKT/mTOR pathway and combination treatment with OMT and OXA would be a promising therapeutic strategy for colon carcinoma treatment.

Keywords

Oxymatrine Colon carcinoma Oxaliplatin Synergistically PI3K/AKT 

Notes

Acknowledgments

This study was supported by the Programfor Young Scientist in Science and Education of Suzhou City (No. KJXW2014053), the Program for Young Scientist in Science and Education of Wujiang District (No. WWK201415).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Yan Liu
    • 1
  • Tingting Bi
    • 2
  • Zheng Wang
    • 1
  • Guoliang Wu
    • 1
  • Liqiang Qian
    • 1
  • Quangen Gao
    • 1
    Email author
  • Genhai Shen
    • 1
  1. 1.Department of General SurgeryWujiang No.1 People’s HospitalSuzhouChina
  2. 2.Department of Geriatric WardWujiang No.1 People’s HospitalSuzhouChina

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