PURPOSE Celecoxib, a highly selective cyclooxygenase-2 inhibitor, regulates apoptosis of several types of human cancer cells. The purpose of this study was to investigate whether celecoxib in combination with paclitaxel modulates apoptosis of ovarian cancer cells, and to identify the signal pathway by which celecoxib mediates apoptosis. MATERIALS AND METHODS OVCAR-3 cells were exposed to paclitaxel (20 microM) in the absence or presence of celecoxib (10 microM). Cell viability was evaluated using a Cell Counting Kit-8 assay. Apoptosis was evaluated using Annexin-V/7-aminoactinomycin D staining and a cellular DNA fragmentation enzyme-linked immunosorbent assay. Caspase-3, -9, and cleavage of poly ADP-ribose polymerase (PARP) were determined by western blotting. Expression of nuclear factor-kappaB (NF-kappaB) and vascular endothelial growth factor (VEGF) and Akt activation were assessed using reverse transcriptase-polymerase chain reaction and western blotting. RESULTS Celecoxib enhanced paclitaxel-induced growth inhibition of OVCAR-3 cells. Celecoxib significantly increased paclitaxel-induced apoptosis of OVCAR-3 cells.
Pretreatment with celecoxib also increased activation of caspase-9, -3 and cleaved PARP following paclitaxel-treatment. Exposure of OVCAR-3 cells to celecoxib in combination with paclitaxel resulted in downregulation of NF-kappaB activation and VEGF expression. Furthermore, combining celecoxib and paclitaxel inhibited phosphorylation of Akt. CONCLUSION OVCAR-3 cells were sensitized to paclitaxel-induced apoptosis by celecoxib through downregulation of NF-kappaB and Akt activation, suggesting that celecoxib may work synergistically with paclitaxel to inhibit different targets and ultimately produce anticancer effects. Combining celecoxib with paclitaxel may prove beneficial in the clinical treatment of ovarian cancer.
Citations
Citations to this article as recorded by
Concomitant effects of paclitaxel and celecoxib on genes involved in apoptosis of triple-negative metastatic breast cancer cells Mohaddeseh Hedayat, Mohammad Rafi Khezri, Reza Jafari, Hassan Malekinejad, Naime Majidi Zolbanin Medical Oncology.2023;[Epub] CrossRef
Hyperforin-mediated anticancer mechanisms in MDA-MB-231 cell line: insights into apoptotic mediator modulation and caspase activation Muttiah Barathan, Ahmad Khusairy Zulpa, Kumutha Malar Vellasamy, Zaridatul Aini Ibrahim, See Mee Hoong, Vanitha Mariappan, Gopinath Venkatraman, Jamuna Vadivelu Journal of Taibah University for Science.2023;[Epub] CrossRef
Celecoxib Reverse Invasion and Metastasis of Gastric Cancer through Lnc_AC006548.28-miR-223-LAMC2 Pathway Guohua Jin, Jianguang Zhang, Tingting Cao, He Zhu, Yang Shi, Kapil Sharma Computational Intelligence and Neuroscience.2022; 2022: 1. CrossRef
New Visions on Natural Products and Cancer Therapy: Autophagy and Related Regulatory Pathways Alma Martelli, Marzieh Omrani, Maryam Zarghooni, Valentina Citi, Simone Brogi, Vincenzo Calderone, Antoni Sureda, Shahrokh Lorzadeh, Simone C. da Silva Rosa, Beniamin Oscar Grabarek, Rafał Staszkiewicz, Marek J. Los, Seyed Fazel Nabavi, Seyed Mohammad Nab Cancers.2022; 14(23): 5839. CrossRef
MicroRNA-758 Regulates Oral Squamous Cell Carcinoma via COX-2 Gang Dong, Hong Chen, Yan Shi, Chunrong Jiang, Hongtao Yang Indian Journal of Surgery.2021; 83(4): 932. CrossRef
Synergistic effects of green tea extract and paclitaxel in the induction of mitochondrial apoptosis in ovarian cancer cell lines Mohammad Panji, Vahideh Behmard, Zahra Zare, Monireh Malekpour, Hasan Nejadbiglari, Saeede Yavari, Tina Nayerpour dizaj, Azadeh Safaeian, Ali Bakhshi, Omid Abazari, Mojtaba Abbasi, Parisa Khanicheragh, Maryam Shabanzadeh Gene.2021; 787: 145638. CrossRef
Spike-in normalization for single-cell RNA-seq reveals dynamic global transcriptional activity mediating anticancer drug response Xin Wang, Jane Frederick, Hongbin Wang, Sheng Hui, Vadim Backman, Zhe Ji NAR Genomics and Bioinformatics.2021;[Epub] CrossRef
Identification of Key Genes and Pathways Associated With Paclitaxel Resistance in Esophageal Squamous Cell Carcinoma Based on Bioinformatics Analysis Zhimin Shen, Mingduan Chen, Fei Luo, Hui Xu, Peipei Zhang, Jihong Lin, Mingqiang Kang Frontiers in Genetics.2021;[Epub] CrossRef
Cyclooxygenase-2 promotes ovarian cancer cell migration and cisplatin resistance via regulating epithelial mesenchymal transition Lin Deng, Ding-qing Feng, Bin Ling Journal of Zhejiang University-SCIENCE B.2020; 21(4): 315. CrossRef
Paclitaxel induces apoptosis through the TAK1–JNK activation pathway Di Yu‐Wei, Zhuo‐sheng Li, Shu‐min Xiong, Ge Huang, Yan‐fei Luo, Tie‐ying Huo, Mao‐hua Zhou, You‐wei Zheng FEBS Open Bio.2020; 10(8): 1655. CrossRef
Integration of genetic variants and gene network for drug repurposing in colorectal cancer Lalu Muhammad Irham, Henry Sung-Ching Wong, Wan-Hsuan Chou, Wirawan Adikusuma, Eko Mugiyanto, Wan-Chen Huang, Wei-Chiao Chang Pharmacological Research.2020; 161: 105203. CrossRef
Correlation between the changes of serum COX 2, APE1, VEGF, TGF-β and TSGF levels and prognosis in patients with osteosarcoma before and after treatment Qingxi Zhang, Guo Dong, Fuchuan Wang, Wenyuan Ding Journal of Cancer Research and Therapeutics.2020; 16(2): 335. CrossRef
Preventative effect of celecoxib in dimethylbenz[a]anthracene-induced ovarian cancer in rats Zhuyan Shao, Qiang Wen, Tao Zhu, Wei Jiang, Yu Kang, Conjian Xu, Shihua Wang Archives of Gynecology and Obstetrics.2018; 298(5): 981. CrossRef
Cyclooxygenase-1 (COX-1) and COX-1 Inhibitors in Cancer: A Review of Oncology and Medicinal Chemistry Literature Alessandra Pannunzio, Mauro Coluccia Pharmaceuticals.2018; 11(4): 101. CrossRef
Targeting multidrug-resistant ovarian cancer through estrogen receptor α dependent ATP depletion caused by hyperactivation of the unfolded protein response Xiaobin Zheng, Neal Andruska, Michael J. Lambrecht, Sisi He, Amadeo Parissenti, Paul J. Hergenrother, Erik R. Nelson, David J. Shapiro Oncotarget.2018; 9(19): 14741. CrossRef
MicroRNA-381 regulates the occurrence and immune responses of coronary atherosclerosis via cyclooxygenase-2 Kaiyou Song, Lianting Li, Guiling Sun, Yanjin Wei Experimental and Therapeutic Medicine.2018;[Epub] CrossRef
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, Wei-Hao Sun Oncotarget.2017; 8(54): 92770. CrossRef
Literature-based discovery of new candidates for drug repurposing Hsih-Te Yang, Jiun-Huang Ju, Yue-Ting Wong, Ilya Shmulevich, Jung-Hsien Chiang Briefings in Bioinformatics.2016; : bbw030. CrossRef
Synergistic growth inhibitory effect of deracoxib with doxorubicin against a canine mammary tumor cell line, CMT-U27 Tülay BAKIREL, Fulya Üstün ALKAN, Oya ÜSTÜNER, Suzan ÇINAR, Funda YILDIRIM, Gaye ERTEN, Utku BAKIREL Journal of Veterinary Medical Science.2016; 78(4): 657. CrossRef
Aberrant over-expression of COX-1 intersects multiple pro-tumorigenic pathways in high-grade serous ovarian cancer Andrew J. Wilson, Oluwole Fadare, Alicia Beeghly-Fadiel, Deok-Soo Son, Qi Liu, Shilin Zhao, Jeanette Saskowski, Md. Jashim Uddin, Cristina Daniel, Brenda Crews, Brian D. Lehmann, Jennifer A. Pietenpol, Marta A. Crispens, Lawrence J. Marnett, Dineo Khabele Oncotarget.2015; 6(25): 21353. CrossRef