{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:46:18Z","timestamp":1787013978909,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,5,22]],"date-time":"2017-05-22T00:00:00Z","timestamp":1495411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31600075"],"award-info":[{"award-number":["31600075"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31620103910"],"award-info":[{"award-number":["31620103910"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91440203"],"award-info":[{"award-number":["91440203"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:p>\n                    Metformin is the most commonly used drug for type 2 diabetes and has potential benefit in treating and preventing cancer. Previous studies indicated that membrane proteins can affect the antineoplastic effects of metformin and may be crucial in the field of cancer research. However, the antineoplastic effects of metformin and its mechanism in gallbladder cancer (\n                    <jats:styled-content style=\"fixed-case\">GBC<\/jats:styled-content>\n                    ) remain largely unknown. In this study, the effects of metformin on\n                    <jats:styled-content style=\"fixed-case\">GBC<\/jats:styled-content>\n                    cell proliferation and viability were evaluated using the Cell Counting Kit\u20108 (\n                    <jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content>\n                    \u20108) assay and an apoptosis assay. Western blotting was performed to investigate related signaling pathways. Of note, inhibition, knockdown and upregulation of the membrane protein Chloride intracellular channel 1 (\n                    <jats:styled-content style=\"fixed-case\">CLIC<\/jats:styled-content>\n                    1) can affect\n                    <jats:styled-content style=\"fixed-case\">GBC<\/jats:styled-content>\n                    resistance in the presence of metformin. Our data demonstrated that metformin apparently inhibits the proliferation and viability of\n                    <jats:styled-content style=\"fixed-case\">GBC<\/jats:styled-content>\n                    cells. Metformin promoted cell apoptosis and increased the number of early apoptotic cells. We found that metformin can exert growth\u2010suppressive effects on these cell lines via inhibition of p\u2010Akt activity and the Bcl\u20102 family. Notably, either dysfunction or downregulation of\n                    <jats:styled-content style=\"fixed-case\">CLIC<\/jats:styled-content>\n                    1 can partially decrease the antineoplastic effects of metformin while upregulation of\n                    <jats:styled-content style=\"fixed-case\">CLIC<\/jats:styled-content>\n                    1 can increase drug sensitivity. Our findings provide experimental evidence for using metformin as an antitumor treatment for gallbladder carcinoma.\n                  <\/jats:p>","DOI":"10.1111\/cas.13248","type":"journal-article","created":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T14:57:14Z","timestamp":1491404234000},"page":"1240-1252","source":"Crossref","is-referenced-by-count":21,"title":["Chloride intracellular channel 1 regulates the antineoplastic effects of metformin in gallbladder cancer cells"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1772-5572","authenticated-orcid":false,"given":"Yongchen","family":"Liu","sequence":"first","affiliation":[{"name":"Department of General Surgery and Laboratory of General Surgery Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"},{"name":"Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine Shanghai 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