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Down-regulation of p110β expression increases chemosensitivity of colon cancer cell lines to oxaliplatin

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Summary

This study examined the synergetic effect of class IA Phosphoinositide 3-kinases catalytic subunit p110β knockdown in conjunction with oxaliplatin treatment on colon cancer cells. Down-regulation of p110β by siRNA interference and oxaliplatin treatment were applied in colon cancer cell lines HT29, SW620 and HCT116. MTT assay was used to measure the inhibitory effect of p110β knockdown on the proliferation of colon cancer cell lines. SubG1 assay and Annexin-V FITC/PI double-labeling cytometry were applied to detect cell apoptosis. And cell cycle was evaluated by using PI staining and flow cytometry. The expression of caspase 3, cleaved PARP, p-Akt, T-Akt and p110β was determined by western blotting. The results suggested that down-regulation of p110β expression by siRNA obviously reduced cell number via accumulation in G0-G1 phase of the cell cycle in the absence of notablely increased apoptosis in colon cancer cell lines HT29 and SW620 (S phase arrest in HCT116). Moreover, inhibition of p110β expression increased oxaliplatin-induced cell apoptosis and cell cycle arrest in HT29, HCT116 and SW620 cell lines. In addition, increases of cleaved caspase-3 and cleaved PARP induced by oxaliplatin treatment were determined by immunoblotting in p110β knockdown group compared with normal control group and wild-type group. It is concluded that down-regulated expression of p110β could inhibit colon cancer cells proliferation and result in increased chemosensitivity of colorectal cancer cells to oxaliplatin through augmentation of oxaliplatin-induced cell apoptosis and cell cycle arrest.

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Authors and Affiliations

  1. Tongji Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Weicheng Liu  (刘韦成), Guihua Wang  (王桂华), Xiaonian Cao  (曹小年), Xuelai Luo  (罗学来), Zhaoming Li  (李兆明), Yu Deng  (邓 豫), Xiaolan Li  (李小兰) & Junbo Hu  (胡俊波)

  2. Departement of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Shijia Wang  (王诗佳), Mengfei Liu  (刘梦菲) & Jing Wang  (王 晶)

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  1. Weicheng Liu  (刘韦成)
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  2. Guihua Wang  (王桂华)
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  3. Xiaonian Cao  (曹小年)
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  4. Xuelai Luo  (罗学来)
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  5. Zhaoming Li  (李兆明)
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  6. Yu Deng  (邓 豫)
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  7. Xiaolan Li  (李小兰)
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  8. Shijia Wang  (王诗佳)
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  9. Mengfei Liu  (刘梦菲)
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  10. Junbo Hu  (胡俊波)
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  11. Jing Wang  (王 晶)
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Corresponding author

Correspondence to Jing Wang  (王 晶).

Additional information

This work was supported by grants from National Natural Science Foundation of China (No. 81072431, 30872472, 30973496, and 30800569), a grant from Innovation Foundation of Huazhong University of Science and Technology (No. 2010MS027), grants of Foundation of Program 973 (No. 2009CB521802), and Special Fund for Central University Basic Scientific Research (No. 2011JC062, and 2011JC063).

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Liu, W., Wang, G., Cao, X. et al. Down-regulation of p110β expression increases chemosensitivity of colon cancer cell lines to oxaliplatin. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 32, 280–286 (2012). https://doi.org/10.1007/s11596-012-0049-z

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  • DOI: https://doi.org/10.1007/s11596-012-0049-z

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