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.

CONCLUSION

PKC regulates multidrug resistance of the cells through mechanisms other than regulation of mRNA level of mdr1 gene.