SP600125, an inhibitor of Jnk pathway, reduces viability of relatively resistant cancer cells to doxorubicin.
We identified four breast cancer cell lines and one stomach cancer cell line resistant to the cytotoxic effects of doxorubicin (DOX) and examined their sensitivity to other chemotherapeutic agents. SP600125, an inhibitor of the Jnk pathway, reduced the cellular viability of all five DOX-resistant cancer cell lines. Jnk1 siRNA also reduced the viability of the one DOX-resistant cell line in which it was tested. Similar results were produced in an in vivo mouse model, in which the volume of tumors derived from the DOX-resistant cell line was reduced more effectively by treatment with SP600125 than by treatment with DOX, whereas those from a DOX-sensitive cell line were reduced only by DOX treatment. Overall, these results may contribute to the development of chemotherapeutic treatments for patients with DOX-resistant tumors.
Kim
Ju-Hwa
JH
Research Institute, National Cancer Center, 809 Madu 1-dong, Ilsan-gu, Goyang-si Gyeonggi-do, Republic of Korea.
Kim
Tae Hyung
TH
Kang
Han Sung
HS
Ro
Jungsil
J
Kim
Hyung Sik
HS
Yoon
Sungpil
S
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D013274:Stomach Neoplasms / Q000201:enzymology
D000873:Anthracenes; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; C432165:pyrazolanthrone; D004317:Doxorubicin; D048031:JNK Mitogen-Activated Protein Kinases; D048055:Mitogen-Activated Protein Kinase 8