Uricase sensitizes hepatocellular carcinoma cells to 5-fluorouracil through uricase-uric acid-UMP synthase axis.
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| Abstract |
Conventional chemotherapy plays a key role in hepatocellular carcinoma (HCC) treatment, however, with intrinsic or acquired chemoresistance being a major constraint. Here, we aimed to identify potential target to reverse such chemoresistance. In the present study, we found significant difference in uridine monophosphate synthetase (UMPS) expression between 5-FU resistant and sensitive HCC cell lines and the overexpression or downregulation of UMPS impacted 5-FU response in HCC cells. We further found that inhibition of UMPS activity with uric acid at concentration present in human plasma decreased the 5-FU sensitivity of HCC cells, while reduction of uric acid levels with uricase improved the 5-FU sensitivity of HCC cells as well as colorectal cancer cells. In vivo studies also suggested that modulation of uric acid levels did affect 5-FU sensitivity of tumors. These data indicated that UMPS was correlated with the 5-FU resistance in HCC cells and uricase sensitized cancer cells to 5-FU through uricase-uric acid-UMP synthase axis, which provided a potential strategy to improve the efficacy of 5-FU-based chemotherapy for human cancers.
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| Authors | Saihong Yu, Zhuduo Li, Linglan Tu, Yiyi Pu, Dongmei Yan, Xiaoju Wang, Xiaoliang Zheng, Jie Yu |
| Journal | Journal of physiology and biochemistry (J Physiol Biochem) Vol. 78 Issue 3 Pg. 679-687 (Aug 2022) ISSN: 1877-8755 [Electronic] Spain |
| PMID | 35674867 (Publication Type: Journal Article) |
| Copyright | © 2022. The Author(s) under exclusive licence to University of Navarra. |
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