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Article

Rab23 promotes the cisplatin resistance of ovarian cancer via the Shh-Gli-ABCG2 signaling pathway

  • Authors:
    • Wenjie Zhang
    • Feng Yu
    • Yu Wang
    • Yu Zhang
    • Lingxin Meng
    • Yuhua Chi
  • View Affiliations / Copyright

    Affiliations: Oncology Department, Rizhao People's Hospital, Rizhao, Shandong 276800, P.R. China, Gynaecology Department, Maternal and Child Health Care and Family Planning Service Center of Rizhao City, Rizhao, Shandong 276826, P.R. China, Emergency Internal Medicine Department, Central Hospital of Rizhao City, Rizhao, Shandong 276800, P.R. China, Blood Drawing Department, Central Blood Station of Rizhao City, Rizhao, Shandong 276800, P.R. China
  • Pages: 5155-5160
    |
    Published online on: February 5, 2018
       https://doi.org/10.3892/ol.2018.7949
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Abstract

As a novel member of the Rab GTPase family, the role of Rab23 has been reported in multiple types of tumor. However, to the best of our knowledge, the role of Rab23 in ovarian cancer (OC) has not yet been reported. In the present study, immunohistochemistry analysis demonstrated that Rab23 was upregulated in OC tissue; survival analysis indicated that Rab23 expression was associated with a reduced overall survival (OS) rate and disease‑free survival (DFS) time. In vitro experiments also demonstrated the increased expression of Rab23 in the OC cells lines, A2780 and SKOV‑3, compared with in the normal ovarian cell line, IOSE80. Following the silencing of ABCG2 in SKOV‑3 cells, ATP‑binding cassette sub‑family G member 2 (ABCG2) expression was significantly downregulated both at the RNA and protein levels. The cisplatin (DDP) IC50 declined from 43.09±7.12 µmol/l in control cells to 26.46±5.38 µmol/l in SKOV‑3 cells with silenced Rab23. In contrast, in A2780 cells overexpressing Rab23 (A2780‑Rab23), ABCG2 expression was significantly upregulated and the DDP IC50 increased from 27.42±6.54 µmol/l in control cells to 45.92±5.23 µmol/l in A2780‑Rab23. Investigation into the potential molecular mechanisms for this revealed that the expression of sonic hedgehog (Shh) and Gli family zinc finger 1 (Gli1) was increased in A2780‑Rab23 cells, whereas silencing Rab23 in SKOV‑3 cells significantly inhibited the expression of Shh and Gli1. The Gli1 inhibitor GANT‑61 significantly abrogated the increased ABCG2 expression in A2780‑Rab23 cells. Furthermore, the DDP IC50 in A2780‑Rab23 cells decreased significantly following the silencing of ABCG2 expression; the IC50 declined from 51.66±8.32 µmol/l in A2780‑Rab23 cells to 25.61±6.17 µmol/l in A2780‑Rab23 cells with silenced ABCG2. Collectively, the results indicate that Rab23 promotes the DDP resistance of OC cells via the Shh‑Gli1‑ABCG2 pathway, providing the proof of principle for the further investigation of drug resistance therapy targeting Rab23.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang W, Yu F, Wang Y, Zhang Y, Meng L and Chi Y: Rab23 promotes the cisplatin resistance of ovarian cancer via the Shh-Gli-ABCG2 signaling pathway. Oncol Lett 15: 5155-5160, 2018.
APA
Zhang, W., Yu, F., Wang, Y., Zhang, Y., Meng, L., & Chi, Y. (2018). Rab23 promotes the cisplatin resistance of ovarian cancer via the Shh-Gli-ABCG2 signaling pathway. Oncology Letters, 15, 5155-5160. https://doi.org/10.3892/ol.2018.7949
MLA
Zhang, W., Yu, F., Wang, Y., Zhang, Y., Meng, L., Chi, Y."Rab23 promotes the cisplatin resistance of ovarian cancer via the Shh-Gli-ABCG2 signaling pathway". Oncology Letters 15.4 (2018): 5155-5160.
Chicago
Zhang, W., Yu, F., Wang, Y., Zhang, Y., Meng, L., Chi, Y."Rab23 promotes the cisplatin resistance of ovarian cancer via the Shh-Gli-ABCG2 signaling pathway". Oncology Letters 15, no. 4 (2018): 5155-5160. https://doi.org/10.3892/ol.2018.7949
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang W, Yu F, Wang Y, Zhang Y, Meng L and Chi Y: Rab23 promotes the cisplatin resistance of ovarian cancer via the Shh-Gli-ABCG2 signaling pathway. Oncol Lett 15: 5155-5160, 2018.
APA
Zhang, W., Yu, F., Wang, Y., Zhang, Y., Meng, L., & Chi, Y. (2018). Rab23 promotes the cisplatin resistance of ovarian cancer via the Shh-Gli-ABCG2 signaling pathway. Oncology Letters, 15, 5155-5160. https://doi.org/10.3892/ol.2018.7949
MLA
Zhang, W., Yu, F., Wang, Y., Zhang, Y., Meng, L., Chi, Y."Rab23 promotes the cisplatin resistance of ovarian cancer via the Shh-Gli-ABCG2 signaling pathway". Oncology Letters 15.4 (2018): 5155-5160.
Chicago
Zhang, W., Yu, F., Wang, Y., Zhang, Y., Meng, L., Chi, Y."Rab23 promotes the cisplatin resistance of ovarian cancer via the Shh-Gli-ABCG2 signaling pathway". Oncology Letters 15, no. 4 (2018): 5155-5160. https://doi.org/10.3892/ol.2018.7949
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