Study Of PKC Enzymatic Activity In Multidrug Resistance Of Human Renal Cell Carcinoma

Renal cell carcinoma (RCC) is a malignant tumor in urology and poor effect to chemotherapy, for there is resistance to some drugs in RCC, and this resistance is called Multidrug resistance (MDR). Resistance character in malignant cell is relate to various factors including the product of mdr1 ( P - glucoprotein or P - gp) and multidrug resistance protein (MRP). Present studies show PKC is a key molecule in tumor appearance,progression-.metastasis and multidrug resistance, PKC is a Ca2 + activating PI - depending protein kinase, and one of key molecule related to signal transition in cell. Additionally, various tumors have a high activity detected, but no report described relationship between MDR in RCC and PKC activity. Present experiment to analyse the PKC activity and the relation to MDR and progression in RCC would provide a new and actual treatment to reverse multidrug resistance to chemotherapy.Methods30 patients come from Department of Urology in China Medical University First Clinical College from August to December in 2001, pathologic diagnosed as renal cell carcinoma after radical operation were collected, 20 males and 10 females ( age range from 32 - 73 ) with mean ages of 52. 8 and without chemotherapy.1. Takai method was performed to detect PKC activity of RCC and adjacent tissue.2. P - gp,MRPmRNA expression by RT - PCR method.Results(1) PKC enzyme has a high activity significantly in both plasma and membrane of Renal cell carcinoma compare to adjacent tissue; and positive correlation to high stages and pathologic grades in RCC. Ratio of membrane/plasma study demonstrate RCC has a high PKC activity ratio M/P than in adjacent area, suggest PKC play a role of PKC membrane translocation in the progression of renal tumor.(2) P - gp mRNA expression found 90% in all tumor tissues, and 100% in all adjacent tissues. RCC have a lower P - gpmRNA expression compared with normal tissues. No difference was shown among various clinical stages; though P - gpmRNA expression was higher in G1 than G2 and G3, but no significant difference was found in pathologic grades; MRPmRNA express in both tumor and normal tissues of all samples, a higher level in tumor than adjacent kidney tissues. And a positive relation with pathologic grades in tumor area, however as same as P - gp no difference in clinical stages was found.(3) correlation between PKC activity and MDR factors in renal cell carcinoma indicate P - gpmRNA no relativity with PKC activity; MRPmRNA has positive relativity with PKC activity, cell plasma and membrane relation coefficient are 0. 36,0.45 respectively,ratio M/P r value is 0.62,relation test show all are significant.Conclusion(1) PKC enzyme has a high activity significantly in both plasma and membrane of Renal cell carcinoma compare to adjacent tissue; and positive correlation to high stages and pathologic grades in RCC. r.(2) RCC have a lower P - gpmRNA expression compared with normal tissues. No difference was shown among various clinical stages and pathologic grades.(3) MRPmRNA express a higher level in tumor than adjacent kidney tissues. And a positive relation with pathologic grades in tumor area, however no difference in clinical stages was found.(4) correlation between PKC activity and MDR factors in renal cell carcinoma indicate P - gpmRNA no relativity with PKC activity; MRPmRNA has positive relativity with PKC activity.