Significance of cyclooxygenase‑2, prostaglandin E2 and CD133 levels in sunitinib‑resistant renal cell carcinoma

Luo,Lei; Liang,Ye; Ding,Xuemei; Ma,Xiaocheng; Zhang,Guiming; Sun,Lijiang

doi:10.3892/ol.2019.10442

Significance of cyclooxygenase‑2, prostaglandin E2 and CD133 levels in sunitinib‑resistant renal cell carcinoma

Authors:
- Lei Luo
- Ye Liang
- Xuemei Ding
- Xiaocheng Ma
- Guiming Zhang
- Lijiang Sun
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Affiliations: Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shangdong 266003, P.R. China, Key Laboratory, Department of Urology and Andrology, The Affiliated Hospital of Qingdao University, Qingdao, Shangdong 266003, P.R. China, Operating Room, The Affiliated Hospital of Qingdao University, Qingdao, Shangdong 266003, P.R. China
Published online on: June 6, 2019 https://doi.org/10.3892/ol.2019.10442
Pages: 1442-1450

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Abstract

The current study investigated the mechanism underlying sunitinib resistance. The parental human renal cell carcinoma (RCC) cell line 786‑O was continuously exposed to various doses of sunitinib to obtain sunitinib‑resistant cells (786‑O/S). Cell proliferation and colony formation assays were performed to assess the survival of 786‑O/S cells. The half‑inhibitory concentration for the drug‑resistant cells was calculated. 786‑O/S cells demonstrated notably morphological changes compared with parental cells. Compared with 786‑O cells, 786‑O/S cells exhibited stronger proliferative and colony‑forming abilities. Western blot analysis was performed to measure the levels of cyclooxygenase 2 (COX‑2) and prostaglandin E2 (PGE2). Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to detect the expression of COX‑2 and cluster of differentiation (CD) 133 in both 786‑O and 786‑O/S cells. Following incubation of the two cell lines with celecoxib, a COX‑2 inhibitor, RT‑qPCR was performed to detect the expression of COX‑2 and CD133, and western blot analysis was used to assess the expression of CD133. The results revealed that the levels of COX‑2 and PGE2 were significantly higher in 786‑O/S cells compared with 786‑O cells (P<0.01). Similarly, the expression of CD133 was 24‑fold higher in 786‑O/S compared with the parental cells (P<0.01). When celecoxib was incubated with the two cell lines, the expression of COX‑2 and CD133 decreased significantly (P<0.0001). In summary, the results indicate that activation of the COX‑2‑PGE2 pathway in RCC leads to the development of sunitinib resistance and may serve an important role in the maintenance of the characteristics of stem cells that are closely associated with drug resistance.

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