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      Novel combination of celecoxib and metformin improves the antitumor effect by inhibiting the growth of Hepatocellular Carcinoma

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          Abstract

          Objective: To explore the effect of COX-2 inhibitor celecoxib in combination with metformin on the prevention of Hepatocellular carcinoma (HCC) and the mechanisms involved.

          Methods: HCC cell lines and an HCC rat model were treated with celecoxib, metformin or a combination of both. Cell viability and tumor formation were measured.

          Results: In vitro and in vivo studies showed that treatment with a combination of celecoxib and metformin inhibited proliferation of HCC to a greater extent than either treatment alone, by reducing the phosphorylation of MTOR.

          Conclusion: The study suggested that celecoxib combined with metformin would be more effective for the preventing occurrence of HCC than either treatment alone and this combination of therapy is worthy of further study.

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          The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis.

          G Steinbach, P M Lynch, R K Phillips … (2000)
          Patients with familial adenomatous polyposis have a nearly 100 percent risk of colorectal cancer. In this disease, the chemopreventive effects of nonsteroidal antiinflammatory drugs may be related to their inhibition of cyclooxygenase-2. We studied the effect of celecoxib, a selective cyclooxygenase-2 inhibitor, on colorectal polyps in patients with familial adenomatous polyposis. In a double-blind, placebo-controlled study, we randomly assigned 77 patients to treatment with celecoxib (100 or 400 mg twice daily) or placebo for six months. Patients underwent endoscopy at the beginning and end of the study. We determined the number and size of polyps from photographs and videotapes; the response to treatment was expressed as the mean percent change from base line. At base line, the mean (+/-SD) number of polyps in focal areas where polyps were counted was 15.5+/-13.4 in the 15 patients assigned to placebo, 11.5+/-8.5 in the 32 patients assigned to 100 mg of celecoxib twice a day, and 12.3+/-8.2 in the 30 patients assigned to 400 mg of celecoxib twice a day (P=0.66 for the comparison among groups). After six months, the patients receiving 400 mg of celecoxib twice a day had a 28.0 percent reduction in the mean number of colorectal polyps (P=0.003 for the comparison with placebo) and a 30.7 percent reduction in the polyp burden (the sum of polyp diameters) (P=0.001), as compared with reductions of 4.5 and 4.9 percent, respectively, in the placebo group. The improvement in the extent of colorectal polyposis in the group receiving 400 mg twice a day was confirmed by a panel of endoscopists who reviewed the videotapes. The reductions in the group receiving 100 mg of celecoxib twice a day were 11.9 percent (P=0.33 for the comparison with placebo) and 14.6 percent (P=0.09), respectively. The incidence of adverse events was similar among the groups. In patients with familial adenomatous polyposis, six months of twice-daily treatment with 400 mg of celecoxib, a cyclooxygenase-2 inhibitor, leads to a significant reduction in the number of colorectal polyps.
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            Metformin in cancer therapy: a new perspective for an old antidiabetic drug?

            Issam Ben Sahra, Yannick Le Marchand-Brustel, Jean-François Tanti … (2010)
            Metformin is the most widely used antidiabetic drug in the world, and there is increasing evidence of a potential efficacy of this agent as an anticancer drug. First, epidemiological studies show a decrease in cancer incidence in metformin-treated patients. Second, metformin decreases insulin resistance and indirectly reduces insulin level, a beneficial effect because insulin promotes cancer cell growth. Third, several reports outline a direct inhibitory effect of metformin on cancer cell growth and an antitumoral action. Finally, metformin activates the AMP activated protein kinase (AMPK) pathway, a major sensor of the energetic status of the cell, which has been proposed as a promising therapeutic target in cancer.
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              Effective breast cancer combination therapy targeting BACH1 and mitochondrial metabolism

              Jiyoung Lee, Ali Yesilkanal, Joseph Wynne … (2019)
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Cancer
                Journal ID (publisher-id): jca
                Title: Journal of Cancer
                Publisher: Ivyspring International Publisher (Sydney )
                ISSN (Electronic): 1837-9664
                Publication date Collection: 2020
                Publication date (Electronic): 14 September 2020
                Volume: 11
                Issue: 21
                Pages: 6437-6444
                Affiliations
                Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Key Laboratory for High-Incidence Tumor Prevention and Treatment, Ministry of Education, Guangxi Medical University Cancer Hospital, Nanning, China.
                Author notes
                ✉ Corresponding authors: Bang-De Xiang and Jian-Hong Zhong, Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, #71, He Di Rd. Nanning 530021, China. Phone: +86-0771-5330855 (office). Fax: +86-0771-5312000. E-mail: xiangbangde@ 123456gxmu.edu.cn (B.-D.X); zhongjianhong@ 123456gxmu.edu.cn (J-H.Z).

                *These authors contributed equally to this work.

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                Publisher ID: jcav11p6437
                DOI: 10.7150/jca.47532
                PMC ID: 7532521
                PubMed ID: 33033527
                SO-VID: 9956149f-04fc-497c-aeca-8cfc9ceccade
                Copyright © © The author(s)
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                Date received : 28 April 2020
                Date accepted : 27 August 2020
                Categories
                Subject: Research Paper

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: celecoxib,metformin,hepatocellular carcinoma,combination,mtor
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: celecoxib, metformin, hepatocellular carcinoma, combination, mtor

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