Effect of protein kinase C on multidrug resistance of multidrug-resistant colorectal cancer LoVo/Adr cells.
OBJECTIVE
To observe the effect of protein kinase C (PKC) on the multidrug resistance of multidrug-resistant colorectal cancer LoVo/Adr cells and explore the mechanism.


METHODS
The changes of PKC activity in LoVo/Adr cells in response to treatment with staurosporine (SP) and phorbol-12-myristate-13-acetate (PMA) were detected by way of 32P incorporation. The effect of PKC on adriamycin uptake in LoVo/Adr cells was detected by flow cytometry. Reverse transcriptase-PCR was utilized to observe the effect of PKC on mdr1 gene expression.


RESULTS
PMA evinced bi-directional regulation of PKC activity in LoVo/Adr cells, and SP significantly inhibited membrane and cytosol fraction of PKC activity. Preincubation with PMA for 30 min caused the uptake of adriamycin to decrease significantly, but when the preincubation was prolonged to 24 h, significant increase occurred in adriamycin uptake. Neither PMA nor SP, however, could affect the expression of mdr1 gene.


CONCLUSIONS
PKC regulates multidrug resistance of the cells through mechanisms other than regulation of mRNA level of mdr1 gene.
Ma
Qiang
Q
Department of Gastroenterology, Nanfang Hospital, First Military Medical University, Guangzhou 510515, China. maqiang@fimmu.com
Zhang
Zhen-Shu
ZS
Zhang
Ya-Li
YL
Wang
Qun-Ying
QY
Lai
Zhuo-Sheng
ZS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D004317:Doxorubicin / Q000493:pharmacokinetics; D004347:Drug Interactions; D018432:Drug Resistance, Multiple / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004317:Doxorubicin; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate