Modulation of multidrug resistance in human ovarian cancer cell lines by inhibition of P-glycoprotein 170 and PKC isoenzymes with antisense oligonucleotides.

Multidrug resistance in human ovarian carcinoma cell lines is caused by the expression of several related proteins, namely P-glycoprotein 170 (Pgp-170), glutathione S-transferase-pi GST-pi), and thymidylate synthase (TS). These proteins seem to be regulated by a common mechanism in which the expression of protein kinase C (PKC) is involved. Additionally, the function of Pgp-170 is dependent on PKC phosphorylation.

Messenger RNA expression of resistance proteins and related factors in human ovarian carcinoma cell lines resistant to doxorubicin, taxol and cisplatin.

Doxorubicin- (OAW-dox, SK-OV-dox), taxol- (OAW-tax, SK-OV-tax) and cisplatin- (SK-OV-cis) resistant cells derived from the parental OAW-42 and SK-OV-3 cell lines were established. OAW-42 sublines showed high resistance, the SK-OV-3 sublines only low resistance. OAW-42 sublines showed a cross-resistance profile typical of multidrug resistance (MDR).

Messenger RNA expression of resistance factors in human tumor cell lines after single exposure to radiation.

Resistance of tumor cells to chemotherapeutic drugs can not only be caused by treatment with antineoplastic agents but also by radiotherapy. The aim of this study was to analyze whether ionizing radiation can influence the mRNA expression of proteins which have been found to be involved in drug resistance of tumor cells. Human tumor cell lines (MCF-7, LXF and Sk-Mel) were treated with single doses of irradiation (5, 10 and 20 Gy).

Resistance proteins in human kidney, breast, ovarian and lung-carcinoma - a comparative-analysis.

The expression of P-glycoprotein (P-170), glutathione S-transferase-pi (GST-pi), dihydrofolate reductase (DHFR) and thymidylate synthase (TS) was analyzed immunohistochemically in human tumors of different origin. The resistance proteins were expressed at varying degree: all kidney carcinomas (n=25), 40 of 56 non-small cell lung carcinomas (NSCLC) (71%), 8 of 15 ovarian carcinomas (53%), 5 of 11 breast carcinomas (46%) and 3 of 14 small cell lung carcinomas (SCLC) (21%) expressed more than one resistance protein. A comparison of the immunohistochemical data with the clinical response rates as reported in literature, demonstrates an evident correlation between the number of resistance proteins and the clinical outcome.