STAT3 signaling pathway in drug-resistant bladder cancer cell line

Abstract

STAT3 signaling pathway is related to the proliferation, apoptosis and metastasis of tumor cells. The relationship between STAT3 and drug resistance is still unknown. We studied the inhibitors in STAT3 pathway and its downstream molecules to analyze the unique effects in drug-resistant bladder cancer cells. qRT-PCR and Western blot were implemented to study the expression level of JAK2, STAT3, p-STAT3, MMP2 and Cyclin D1 in Pumc-91 and Pumc-91/ADM cell lines, respectively. The effects of AG490 on the expression of STAT3, p-STAT3, MMP2 and Cyclin D1 in Pumc-91 were evaluated using qRT-PCR and Western blot. Pumc-91/ADM cells were treated with AG490. CCK-8 and wound healing assay were used to detect the cell proliferation and metastasis. Compared to Pumc-91, an obvious decrease of JAK2, p-STAT3 and increase of MMP2 were shown in Pumc-91/ADM cell line. After inhibition of STAT3 signaling pathway, the mRNA and protein levels of STAT3, p-STAT3, MMP2 and Cyclin D1 obviously decreased in the test group. The proliferation and migration of Pumc-91/ADM were suppressed by inhibiting of STAT3. STAT3 pathway regulated the proliferation and migration of bladder cancer drug-resistant cells by modulating the expression of Cyclin D1 and MMP2.

Keywords: bladder cancer; drug resistance bladder cancer; signal transducer and activator of transcription 3(STAT3) AG490; signaling pathway.