Cancer Chemother Pharmacol. 2019 Jul;84(1):187-194. doi:10.1007/s00280-019-03873-8.

Long non-coding RNA GHET1 contributes to chemotherapeutic resistance to Gemcitabine in bladder cancer

Bo Li  1 Dalon Xie  2 Hui Zhang  3

  • 1 Department of Urinary Surgery, Shengjing Hospital, China Medical University, No. 36 Sanhao Street, Heping Area, Shenyang, 100004, China.
  • 2 Department of Anatomy, College of Basic Medical Science, China Medical University, Shenyang, 110001, China.
  • 3 Department of Urinary Surgery, Shengjing Hospital, China Medical University, No. 36 Sanhao Street, Heping Area, Shenyang, 100004, China. zhangh10@sj-hospital.org.

Abstract

Purpose: Bladder cancer (BC) ranks first in the incidence of urogenital tumors in China and second only to prostate cancer in the West. This study will clarify the roles and mechanism of lncRNA GHET1 in chemotherapeutic resistance of BC to Gemcitabine.

Methods: The expression of GHET1 was examined using real-time quantitative PCR. Cell Counting Kit-8 assay was applied to analyze cell proliferation and Gemcitabine sensitivity. Cell apoptosis was detected using Annexin V-FITC/PI double-stained flow cytometry. The expression of ABCC1 protein was examined using Western blotting.

Results: Firstly, the expression of GHET1 was up-regulated in BC, its high expression was relevant to high grade and muscle invasion of BC patients. Secondly, high expression of GHET1 was related to low Gemcitabine sensitivity of BC patients, and GHET1 was highly expressed in Gemcitabine-resistant BC cell lines. Thirdly, knockdown of GHET1 decreased the IC50 of Gemcitabine in Gemcitabine-resistant BC cell lines and advanced the Gemcitabine-induced cytotoxicity; GHET1 promoted Gemcitabine resistance in BC. Finally, knockdown of GHET1 also inhibited the expression of ABCC1 protein in Gemcitabine-resistant BC cells.

Conclusions: High expression of GHET1 was related with the low sensitivity to Gemcitabine of BC; GHET1 contributed to chemotherapeutic resistance to Gemcitabine in BC through up-regulating ABCC1 expression. Our findings are helpful to expound the molecular mechanism of chemotherapeutic resistance in BC.

Keywords: Bladder cancer; Chemotherapeutic resistance; GHET1; Gemcitabine; Long noncoding RNA.

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