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. 1997 Dec;88(12):1211–1217. doi: 10.1111/j.1349-7006.1997.tb00351.x

The Role of Glucuronidation in 7‐Ethyl‐10‐hydroxycamptothecin Resistance in vitro

Toshiaki Takahashi 1, Yasuhiro Fujiwara 1,2,✉, Michio Yamakido 1, Osamu Katoh 3, Hiromitsu Watanabe 3, Peter I Mackenzie 4
PMCID: PMC5921346  PMID: 9473740

Abstract

Although glucuronidation catalyzed by uridine 5′‐diphosphoglucuronosyltransferase (UGT) is a major pathway of drug inactivation in humans, glucuronidation in malignant cells has received little attention as a cause of anti‐cancer drug resistance. In this study, we tried to elucidate the role of SN‐38 glucuronidation in the CPT‐11‐resistant human lung cancer cell line PC‐7/CPT. PC‐7/CPT cells possessed an increased activity to glucuronidate SN‐38 compared to the parent cells, PC‐7, Furthermore, sensitivity of PC‐7/CPT cells to SN‐38 was improved by inhibiting UGT activity. Western and northern blot analyses demonstrated that this increased activity was due to increased levels of UGT protein and mRNA. These results not only imply that npregulation of UGT activity in PC‐7/CPT cells may contribute in part to SN‐38 resistance, hut also illustrate the importance of drug metabolism within malignant cells themselves, as a cause of drug resistance

Keywords: UDP‐glucuronosyltransferase, Drug resistance, CPT‐11, SN‐38, Lung cancer

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The names of UDP glucuronosyltransferase forms are those recommended by a subcommittee of the IUBMB‐IUPHAR Nomenclature Committee and supported by participants at the 8th International Workshop on Glucurouidation and the UDP Glucnronosyltransferases held in Iowa City, Iowa, May, 1996.

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