Research Papers:

Cyclooxygenase-2 mediated synergistic effect of ursolic acid in combination with paclitaxel against human gastric carcinoma

Xian Xu, Guo-Qin Zhu, Kai Zhang, Yi-Chan Zhou, Xiao-Lin Li, Wei Xu, Hao Zhang, Yun Shao, Zhen-Yu Zhang and Wei-Hao Sun _

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Oncotarget. 2017; 8:92770-92777. https://doi.org/10.18632/oncotarget.21576

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Xian Xu1,2, Guo-Qin Zhu1, Kai Zhang3, Yi-Chan Zhou1, Xiao-Lin Li1, Wei Xu1, Hao Zhang1, Yun Shao1, Zhen-Yu Zhang2 and Wei-Hao Sun1

1Department of Geriatric Gastroenterology, The First Affiliated Hospital to Nanjing Medical University, Nanjing 210029, China

2Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China

3Department of Geriatric, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China

Correspondence to:

Wei-Hao Sun, email: [email protected], [email protected]

Keywords: ursolic acid, paclitaxel, gastric cancer, apoptosis, cyclooxygenase-2

Received: June 15, 2017     Accepted: September 03, 2017     Published: October 06, 2017


Ursolic acid (UA) induces apoptosis in gastric cancer cells by inhibiting cyclooxygenase-2 (COX-2). Paclitaxel (PTX) is an important chemotherapy agent used to treat solid tumors. We evaluated the in vitro antitumor activity of UA in combination with PTX against gastric cancer cells and investigated the mechanisms underlying the combined effects. A cytotoxicity test and flow cytometry were utilized to study the effects of UA and PTX on proliferation and apoptosis, respectively. To further elucidate the mechanism, Western blot analysis was used to assess changes in the expression of a series of related proteins, including COX-2, proliferating cell nuclear antigen (PCNA), Bcl-2, and Bax. UA and PTX dose- and time-dependently inhibited BGC-823 and SGC-7901 gastric cancer cell proliferation. Combined delivery of UA and PTX synergistically reduced cell proliferation and induced apoptosis in these cells by lowering COX-2, PCNA, and Bcl-2 expression and by increasing Bax expression. These results indicate that the synergistic inhibition of proliferation and induction of apoptosis by UA and PTX may be induced by reducing COX-2 expression in gastric cancer cells.

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