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Natural resistance to apoptosis correlates with resistance to chemotherapy in colorectal cancer cells

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Abstract

Defects in apoptotic machinery vary among individual cancer cells, and the efficacy of chemotherapy in killing cancer cells depends on the successful induction of apoptosis. This study tested the hypothesis that the intrinsic ability of a cancer cell’s natural resistance to apoptosis would indicate its ability in resistance to chemotherapy. Four widely studied human colorectal cancer cell lines, SW480, HT-29, LoVo and Caco-2, were examined for their apoptotic fates in spontaneous cultures for up to 6 days using flowcytometry. Chemoresponse of these cells was tested against anti-colorectal cancer drugs 5-fluorouracil (5-FU) and oxaliplatin (OXP) at different peak plasma concentrations (PPCs) using MTT assay. Apoptosis analyses demonstrated that, from Day 2 to Day 6 in spontaneous cultures, SW480 and HT-29 lines showed resistance to apoptosis by having much less average early and late apoptotic cells than LoVo and Caco-2 lines with differences of 3.2- to 5.2-fold. Interestingly, apoptosis-resistant SW480 and HT-29 exhibited higher chemoresistance to both 5-FU (P < 0.01 at 5×, 10×, and 50× PPC) and OXP (P < 0.01 at 5× and 10× PPC, and P < 0.05 at 50× PPC) than LoVo and Caco-2. Colorectal cancer cells’ natural resistance to apoptosis is an intrinsic ability that correlates with resistance to chemotherapeutic drugs 5-FU and OXP. Cancer cells’ natural apoptotic phenotypes may help predict the outcome of chemotherapy in colorectal cancers.

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Acknowledgments

This work was supported in part by grants from the Oasis Scholar Fund of Shihezi University (0263-6000601) and the Ministry of Science and Technology of China (2009BAI82B02, 2009BAI82B03).

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Authors and Affiliations

  1. Department of Pathology/the Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, 59 North 2nd Road, Shihezi, 832002, Xinjiang, China

    Yan Zhang, Jia Yuan, Dilixia Simayi, Pin Dong Li, Ying Hong Wang, Feng Li & Wen Jie Zhang

  2. Department of Immunology, Xi’an Center for Disease Control and Prevention, Xi’an, Shanxi, China

    Hong Yan Zhang

  3. Center for Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Wen Jie Zhang

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  1. Yan Zhang
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  2. Jia Yuan
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  3. Hong Yan Zhang
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  5. Pin Dong Li
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  7. Feng Li
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  8. Wen Jie Zhang
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Corresponding author

Correspondence to Wen Jie Zhang.

Additional information

Y. Zhang and J. Yuan contributed equally to this work.

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Zhang, Y., Yuan, J., Zhang, H.Y. et al. Natural resistance to apoptosis correlates with resistance to chemotherapy in colorectal cancer cells. Clin Exp Med 12, 97–103 (2012). https://doi.org/10.1007/s10238-011-0146-5

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  • DOI: https://doi.org/10.1007/s10238-011-0146-5

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