TY - JOUR
T1 - The role of glucuronidation in 7-ethyl-10-hydroxycamptothecin resistance in vitro
AU - Takahashi, Toshiaki
AU - Fujiwara, Yasuhiro
AU - Yamakido, Michio
AU - Katoh, Osamu
AU - Watanabe, Hiromitsu
AU - Mackenzie, Peter I.
PY - 1997/1/1
Y1 - 1997/1/1
N2 - 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 upregulation of UGT activity in PC-7/CPT cells may contribute in part to SN-38 resistance, but also illustrate the importance of drug metabolism within malignant cells themselves, as a cause of drug resistance.
AB - 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 upregulation of UGT activity in PC-7/CPT cells may contribute in part to SN-38 resistance, but also illustrate the importance of drug metabolism within malignant cells themselves, as a cause of drug resistance.
KW - CPT-11
KW - Drug resistance
KW - Lung cancer
KW - SN-38
KW - UDP-glucuronosyltransferase
UR - http://www.scopus.com/inward/record.url?scp=0031473370&partnerID=8YFLogxK
U2 - 10.1111/j.1349-7006.1997.tb00351.x
DO - 10.1111/j.1349-7006.1997.tb00351.x
M3 - Article
C2 - 9473740
AN - SCOPUS:0031473370
VL - 88
SP - 1211
EP - 1217
JO - Japanese Journal of Cancer Research
JF - Japanese Journal of Cancer Research
SN - 0910-5050
IS - 12
ER -