S Kawakami1, Y Kageyama, Y Fujii, K Kihara, H Oshima. 1. Department of Urology and Reproductive Medicine, Graduate School, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-Ku, Tokyo 113-8519, Japan. s-kawakami@med.tmd.ac.jp
Abstract
BACKGROUND: MMPs play a crucial role in the process of cancer invasion and metastasis. METHODS: The influence of NAC on invasion and MMP-9 production of human bladder cancer cell line T24 was investigated using an in vitro invasion assay, gelatin zymography, Western and Northern blot analyses and RT-PCR assays. RESULTS: TPA increased the number of invading T24 cells through reconstituted basement membrane more than 10-fold compared to basal condition. NAC inhibited TPA-enhanced invasion dose-dependently. TPA increased the MMP-9 production by T24 cells without altering expression of TIMP-1 gene, while NAC suppressed TPA-enhanced production of MMP-9. Neither TPA nor NAC altered TIMP-1 mRNA level in T24 cells. In vitro experiments demonstrated that MMP-9 was directly inhibited by NAC but was not influenced by TPA. CONCLUSION: NAC limits invasion of T24 human bladder cancer cells by inhibiting the MMP-9 production in addition to a direct inhibition of MMP-9 activity.
BACKGROUND:MMPs play a crucial role in the process of cancer invasion and metastasis. METHODS: The influence of NAC on invasion and MMP-9 production of humanbladder cancer cell line T24 was investigated using an in vitro invasion assay, gelatin zymography, Western and Northern blot analyses and RT-PCR assays. RESULTS:TPA increased the number of invading T24 cells through reconstituted basement membrane more than 10-fold compared to basal condition. NAC inhibited TPA-enhanced invasion dose-dependently. TPA increased the MMP-9 production by T24 cells without altering expression of TIMP-1 gene, while NAC suppressed TPA-enhanced production of MMP-9. Neither TPA nor NAC altered TIMP-1 mRNA level in T24 cells. In vitro experiments demonstrated that MMP-9 was directly inhibited by NAC but was not influenced by TPA. CONCLUSION:NAC limits invasion of T24 humanbladder cancer cells by inhibiting the MMP-9 production in addition to a direct inhibition of MMP-9 activity.