[Uptake and distribution of adriamycin in multidrug-resistant LoVo/Adr cells].
OBJECTIVE
To investigate adriamycin (Adr) uptake and distribution features in multidrug-resistant LoVo/Adr cells and explore the drug-resistance mechanism of the cells.


METHODS
Adr uptake in LoVo/Adr cells was observed by flow cytometry and the distribution of the drug examined by fluorescence microscope. Immunohistochemical method was employed to detect the expression of P-glycoprotein (P-gp) by the cells.


RESULTS
In comparison with that in LoVo/Adr cells, Adr level in LoVo cells was significantly higher, but after treatment with verapamil, the former cells showed an increased Adr level. Adr distributed mainly in the nucleus in the drug-sensitive LoVo cells, with only a small quantity in the cytoplasm, while in multidrug-resistant LoVo/Adr cells, significantly reduction of Adr quantity in the nucleus and relative increase in the cytoplasm were observed. In response to verapamil treatment, the Adr uptake in LoVo/Adr cells increased and the distribution of the drug was similar to that in sensitive cells. P-gp expression was positive in LoVo/Adr cells, while negative in LoVo cells.


CONCLUSIONS
Abnormal Adr uptake and distribution in drug-resistant cells is related to P-gp expression which is one of the mechanisms for multidrug resistance.
Ma
Qiang
Q
Institute for Digestive Diseases of PLA, Nanfang Hospital, First Military Medical University, Guangzhou 510515, China.
Zhang
Zhen-Shu
ZS
Zhong
Shi-Shun
SS
Lai
Zhuo-Sheng
ZS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D004317:Doxorubicin / Q000493:pharmacokinetics*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004317:Doxorubicin; D014700:Verapamil