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• W3192336000 endingPage "3536" @default.
• W3192336000 startingPage "3515" @default.
• W3192336000 abstract "Gemcitabine is often recommended as a first-line treatment for patients with metastatic pancreatic cancer. However, gemcitabine resistance is a major challenge in the treatment of pancreatic ductal adenocarcinoma. Our group serendipitously identified the role of doxycycline as a potentiator of gemcitabine efficacy in pancreatic cancer cells. Doxycycline and gemcitabine co-treatment was significantly more cytotoxic to pancreatic cancer cells compared to gemcitabine alone. Interestingly, doxycycline only exerted synergistic effects when coupled with gemcitabine as opposed to other conventional chemotherapeutics including nucleoside analogs. The anti-clonogenic effects of gemcitabine on pancreatic cancer cells were also enhanced by doxycycline. According to cell cycle analyses, doxycycline prolonged gemcitabine-mediated S phase cell cycle arrest. Further, gene expression profiling analyses indicated that a small set of genes involved in cell cycle regulation were uniquely modulated by gemcitabine and doxycycline co-treatment compared to gemcitabine alone. Western blot analyses indicated that several cell cycle-related proteins, including cyclin D1, p21, and DNA damage inducible transcript 4 (DDIT4), were further modulated by doxycycline and gemcitabine co-treatment. Taken together, our findings indicate that doxycycline enhances the effects of gemcitabine on cell cycle progression, thus rendering pancreatic cancer cells more sensitive to gemcitabine. However, additional studies are required to assess the mechanisms of doxycycline and gemcitabine synergism, which might lead to novel treatment options for pancreatic cancer." @default.
• W3192336000 created "2021-08-16" @default.
• W3192336000 creator A5008294682 @default.
• W3192336000 creator A5011902291 @default.
• W3192336000 creator A5018057046 @default.
• W3192336000 creator A5026472318 @default.
• W3192336000 creator A5057283425 @default.
• W3192336000 date "2021-07-15" @default.
• W3192336000 modified "2023-09-24" @default.
• W3192336000 title "Doxycycline potentiates the anti-proliferation effects of gemcitabine in pancreatic cancer cells." @default.
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