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In vitro study of human mutL homolog 1 hypermethylation in inducing drug resistance of esophageal carcinoma

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Abstract

Background

Aberrant promoter methylation of tumor suppressor gene can inhibit corresponding protein expression and promote carcinogenesis. Many studies have demonstrated that human mutL homolog 1(hMLH1) promoter methylation is correlated with occurrence and progression of multiple types of tumors. However, its correlation with esophageal carcinoma drug resistance is still unknown.

Aims

To confirm methylation status of hMLH1 promoter in drug-resistance cell line of esophageal carcinoma, further confirm whether hMLH1 promoter methylation is responsible for drug resistance.

Methods

Two stable esophageal carcinoma drug-resistance cell lines were successfully established by Cisplatin (DDP) concentration increment method; methylation status of hMLH1 promoter, mRNA and protein expression of hMLH1 were detected by methylation-specific PCR (MSP), RT-PCR and western blot, respectively; Drug-resistance ability assay was used to detect drug-resistance ability.

Results

Stronger methylation status of hMLH1 promoter, lower hMLH1 mRNA and protein expression were found in both drug-resistance cell lines; after removing methylated bands using 5-aza-2′-deoxycytidine(5-Aza-CdR) in drug-resistance cell lines, hMLH1 mRNA and protein expression were restored and drug-resistance abilities declined nearly by half.

Conclusion

hMLH1 promoter hypermethylation plays important roles in esophageal carcinoma drug-resistance and show us the prospect that combination of demethylation treatment with conventional chemotherapy drugs may bring better therapy effect.

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    Authors and Affiliations

    1. Department of Thoracic Surgery, Central Hospital of Zaozhuang Mining Group of Shandong Province, Zaozhuang, 277800, Shandong, People’s Republic of China

      Y. Cao, Y. Chen & Y. Huang

    2. Second Department of Liver Failure, No. 302 Hospital of PLA, Beijing, 100000, People’s Republic of China

      Z. Liu

    3. Department of Oncology, Affiliated Hospital of Weifang Medical University, #465 Yu He Road, Weifang, 261000, Shandong, People’s Republic of China

      G. Li

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    1. Y. Cao
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    2. Y. Chen
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    3. Y. Huang
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    4. Z. Liu
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    5. G. Li
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    Corresponding author

    Correspondence to G. Li.

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    This study was not funded by any grant.

    Conflict of interest

    Author Yang Cao declares that he has no conflict of interest. Author Yu Chen declares that he has no conflict of interest. Author Yixuan Huang declares that he has no conflict of interest. Author Zifeng Liu declares that she has no conflict of interest. Author Guixin Li declares that he has no conflict of interest.

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    This article does not contain any studies with human participants or animals performed by any of the authors.

    Additional information

    Y. Cao and Y. Chen provided equal contribution to this study.

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    Cao, Y., Chen, Y., Huang, Y. et al. In vitro study of human mutL homolog 1 hypermethylation in inducing drug resistance of esophageal carcinoma. Ir J Med Sci 186, 257–263 (2017). https://doi.org/10.1007/s11845-016-1401-2

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    • DOI: https://doi.org/10.1007/s11845-016-1401-2

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