[Tyrosine kinase inhibitor reverses adriamycin resistance mediated by cell adhesion in RPMI8226 cells].
To study the effects of tyrosine-kinase inhibitor STI571 on the adhesion of RPMI8226 cells to fibronectin (FN), cell adhesion mediated adriamycin-resistance and the Rac1 mRNA expression, the adhesion of RPMI8226 cells to fibronectin and drug resistance mediated by cell adhesion were determined by means of crystal violet staining and MTT assays respectively, Rac1 mRNA levels in RPMI8226 cells were examined by semi-quantitative RT-PCR. The results showed that STI571 could inhibit the adhesion of RPMI8226 cells to fibronectin. When RPMI8226 cells had been adhered to FN or BSA-coated wells for 1, 6 and 12 hours, the adhesion rates were (43.71 +/- 2.18)%, (55.63 +/- 1.56)%, and (63.42 +/- 2.46)% respectively. After treatment with STI571 20 micromol/L, the adhesion rates decreased to (15.12 +/- 1.04)%, (17.58 +/- 1.32)% and (17.24 +/- 1.59)% respectively (P < 0.05). The experiment revealed that growth of RPMI8226 cells adhered to FN-coated plates had a significant advantage over growth on BSA-coated plates when exposed to adriamycin (Adr) for 1 hour followed by a 24-hour culture period, and the mean IC(50) value for FN-adhered cells was (1.46 +/- 0.04) micromol/L while mean IC(50) value for BSA control was (0.78 +/- 0.03) micromol/L (P < 0.05). Following treatment with 20 micromol/L STI571, the mean IC50 values for FN and BSA adhered cells were (0.81 +/- 0.05) micromol/L, (0.74 +/- 0.02) micromol/L respectively, there was no significant difference between them (P > 0.05). RT-PCR demonstrated that the relative Rac1 mRNA level (Rac1/GAPDH) in RPMI8226 cells was downregulated following being treated with 20 micromol/L STI571. It is concluded that STI571 can inhibit the adhesion of RPMI8226 cells to fibronectin, reverse cell adhesion mediated adriamycin-resistance, and downregulate Rac1 mRNA level.
Pan
Yao-Zhu
YZ
Department of Hematology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032 China.
Chen
Xie-Qun
XQ
Gao
Guang-Xun
GX
Gu
Hong-Tao
HT
Zhang
Yong-Qing
YQ
Dong
Bao-Xia
BX
Bai
Qing-Xan
QX
Zhu
Hua-Feng
HF
D001549:Benzamides; D002448:Cell Adhesion; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D000068877:Imatinib Mesylate; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D010879:Piperazines; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured; D020830:rac1 GTP-Binding Protein / Q000096:biosynthesis / Q000235:genetics
D001549:Benzamides; D005353:Fibronectins; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D004317:Doxorubicin; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D020830:rac1 GTP-Binding Protein