Tetramethylpyrazine reduces prostate cancer malignancy through inactivation of the DPP10‑AS1/CBP/FOXM1 signaling pathway

Abstract

Tetramethylpyrazine (TMP), a Chinese herbal medicine, has been reported to possess anticancer effects. Emerging evidence suggests that various long noncoding RNAs (lncRNAs) serve important roles in cancer initiation and progression. In the present study, the tumor-suppressive effects of TMP in human PCa cells was examined and the underlying mechanisms of its actions were determined. The data showed that TMP treatment reduced cell viability and increased apoptosis in a dose-dependent manner. Reverse transcription-quantitative PCR showed TMP treatment increased the expression of lncRNA DPP10-AS1 in PCa cells. Furthermore, DPP10-AS1 was also upregulated in TMP-resistant PCa cells. Knockdown of DPP10-AS1 reversed TMP resistance, whereas increased expression of DPP10-AS1 abrogated the TMP-mediated cytotoxicity in PCa cells. In addition, forkhead box M1 (FOXM1) was verified as the functional target of DPP10-AS1, and knockdown of FOXM1 reversed the TMP/DPP10-AS1-induced cell cytotoxicity. Mechanistically, DPP10-AS1 was associated with CREB binding protein, thereby induced H3K27ac enrichment at the promoter region of the FOXM1 gene. In conclusion, the present study showed that TMP may be a promising treatment agent for PCa and lncRNA DPP10-AS1 may be a promising therapeutic target for TMP treatment.