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Abstract LB-399: Aspirin reduces doxorubicin-induced senescence and early-aging in mice

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Survivors of childhood cancers are often associated with the adverse late effects of earlier cancer treatments, including hearing loss, early menopause, osteoporosis, hypoplasia, fatigue, and infertility. While an accumulating body… Click to show full abstract

Survivors of childhood cancers are often associated with the adverse late effects of earlier cancer treatments, including hearing loss, early menopause, osteoporosis, hypoplasia, fatigue, and infertility. While an accumulating body of evidence supports the hypothesis that cancer treatment is associated with accelerated aging, the mechanisms that lead to a functional decline or frailty remain elusive. Expression of cyclooxygenase-2 (COX2), a key enzyme in prostaglandin biosynthesis, is known to be increased in the tissues of aged humans and mice. We have previously found that transgenic expression of COX2 causes premature aging phenotypes in mice. Since it is well-known that COX2 expression is highly induced by various chemotherapeutic agents, we further investigated the possible link between COX2 and the late effects of chemotherapy. Treatment of juvenile mice with doxorubicin (DOX), an anthracycline-based chemotherapeutic agent, resulted in increased cellular senescence and premature aging in adult mice. Interestingly, tissue expression of COX2 persisted even at 11 weeks after cessation of DOX treatment. In addition, aspirin, a classical non-steroidal anti-inflammatory drug (NSAID), alleviated cellular senescence and early aging phenotypes in DOX-treated mice. Moreover, NSAIDs, either a selective or non-selective COX2 inhibitors, reduced the viability of senescent cells and down-regulated the levels of Bcl-xL and LC3b. Our results suggest that chemotherapy-induced COX2 may play an important role in the late effects of chemotherapy by inducing cellular senescence and further aging. Citation Format: Mingxiao Feng, Minsub Shim. Aspirin reduces doxorubicin-induced senescence and early-aging in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-399.

Keywords: senescence early; senescence; early aging; mice; cox2; cancer

Journal Title: Cancer Research
Year Published: 2018

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