Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Chlorophenyl-benzoxime inhibits pancreatic cancer cell proliferation, invasion and migration by down-regulating the expressions of interleukin-8 and cyclooxygenase-2

Pinyan Wang¹, Yanan Xue², Xiao Yu¹

¹Department of Hepatopancreatobiliary Surgery; ²Department of Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, 421000,China.

For correspondence:- Xiao Yu Email: xyposes@yahoo.com Tel:+8613077304048

Accepted: 21 June 2019 Published: 28 July 2019

Citation: Wang P, Xue Y, Yu X. Chlorophenyl-benzoxime inhibits pancreatic cancer cell proliferation, invasion and migration by down-regulating the expressions of interleukin-8 and cyclooxygenase-2. Trop J Pharm Res 2019; 18(7):1413-1418 doi: 10.4314/tjpr.v18i7.7

© 2019 The authors.
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Abstract

Purpose: To investigate the effects of chlorophenyl-benzoxime (CPBZX) on pancreatic cancer (PC) cell proliferation, invasion and migration, and the underlying mechanism of action.

Methods: Pancreatic carcinoma cell lines (HuP-T4, HuP-T3 and BxPC-3) were cultured in Dulbecco's Modified Eagle medium (DMEM) containing 10 % fetal bovine serum (FBS), penicillin (100 U/mL) and streptomycin (10 μg/mL) at 37 I0;C in a humidified atmosphere containing 5 % CO₂ and 95 % air. Cell proliferation was assessed using MTT assay. Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting were employed for the determination of changes in the levels of expression of carcinoembryonic antigen (CEA), interleukin-8 (IL-8) and cyclooxygenase-2 (COX 2). Cell invasion and migration were determined using Transwell and wound healing assays, respectively.

Results: The results of MTT assay showed that CPBZX significantly and dose-dependently inhibited the proliferation of PC cells (p < 0.05). Incubation of HuP-T4 cells with CPBZX significantly and dose-dependently reduced the invasive ability of the cells (p < 0.05). The migratory ability of HuP-T4 cells was also significantly and dose-dependently inhibited by CPBZX (p < 0.05). The results of Western blotting and qRT PCR showed that CPBZX treatment significantly and dose-dependently upregulated CEA mRNA expression (p < 0.05). On the other hand, the expressions of IL-8 and COX-2 were significantly and dose-dependently down-regulated by CPBZX. Treatment of pancreatic tumor mice with CPBZX significantly decreased tumor growth and metastasis of tumor cells to the pulmonary tissues, liver and lymph nodes (p < 0.05).

Conclusion: The results of this study suggest that CPBZX inhibits the development and metastasis of PC via the down-regulation of IL-8 and COX 2 expressions, and therefore may find application in pancreatic cancer therapy.

Keywords: Pancreatic cancer, Chlorophenyl-benzoxime, Cyclooxygenase, Interleukin-8, Proliferation