Abstract
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.
Highlights
Gastric cancer, one of the most common cancers worldwide, is the second leading cause of cancer deaths [1, 2]
Combined delivery of Ursolic acid (UA) and PTX synergistically reduced cell proliferation and induced apoptosis in these cells by lowering COX-2, proliferating cell nuclear antigen (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
PTX is frequently used in patients with gastric cancer [28, 29], this agent has limited efficacy and has side effects [24]
Summary
One of the most common cancers worldwide, is the second leading cause of cancer deaths [1, 2]. UA inhibits the growth of gastric cancer cells and colon cancer cells [8,9,10]. We found that UA induces apoptosis via down-regulation of cyclooxygenase-2 (COX-2) in gastric cancer cells [10]. COX-2 is expressed in gastric cancer and is a factor in cancer cell proliferation and apoptosis, cancer invasiveness, and metastasis [14, 15]. Studies have shown that COX-2 inhibition by selective COX-2 inhibitors or small interfering RNA (siRNA) suppresses cell growth and leads to apoptosis in human gastric adenocarcinoma cells [16, 17]. Prasad et al [18] reported that UA inhibits the growth of human pancreatic cancer and enhances the antitumor potential of gemcitabine
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