Article Publish Status: FREE
Abstract Title:

Role of Metastasis-Related Genes in Cisplatin Chemoresistance in Gastric Cancer.

Abstract Source:

Int J Mol Sci. 2019 Dec 30 ;21(1). Epub 2019 Dec 30. PMID: 31905926

Abstract Author(s):

Yukiko Nishiguchi, Naohide Oue, Rina Fujiwara-Tani, Takamitsu Sasaki, Hitoshi Ohmori, Shingo Kishi, Shiori Mori, Takuya Mori, Naoya Ikeda, Sohei Matsumoto, Kohei Wakatsuki, Yi Luo, Wataru Yasui, Masayuki Sho, Hiroki Kuniyasu

Article Affiliation:

Yukiko Nishiguchi


The role of metastasis-related genes in cisplatin (CDDP) chemoresistance in gastric cancer is poorly understood. Here, we examined the expression of four metastasis-related genes (namely,,,,) in 39 cases of gastric cancer treated with neoadjuvant therapy with CDDP or CDDP+5-fluorouracil and evaluated its association with CDDP responsiveness. Comparison of CDDP-sensitive cases with CDDP-resistant cases, the expression of c-met, HMGB1, and PCDHB9 was correlated with CDDP resistance. Among them, the expression of HMGB1 showed the most significant correlation with CDDP resistance in multivariate analysis. Treatment of TMK-1 and MKN74 human gastric cancer cell lines with ethyl pyruvate (EP) or tanshinone IIA (TAN), which are reported to inhibit HMGB1 signaling, showed a 4-5-fold increase in inhibition by CDDP. Treatment with EP or TAN also suppressed the expression of TLR4 and MyD88 in the HMGB1 signal transduction pathway and suppressed the activity of NFκB in both cell lines. These results suggest that the expression of these cancer metastasis-related genes is also related to anticancer drug resistance and that suppression of HMGB1 may be particularly useful for CDDP sensitization.

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