Abstract

Abstract Background and Objective: Breast cancer is the malignant tumor with the highest incidence and the second highest mortality among women, and the incidence of breast cancer in China is increasing year by year. The treatment of breast cancer includes radiotherapy, chemotherapy, endocrine therapy, biological targeted therapy and traditional Chinese medicine adjuvant therapy; but the efficacy still needs to be further improved to benefit the patients. Thymoquinone (TQ) is a key component of black grass seed oil and has anti-cancer properties in a variety of tumors. Preliminary studies in our laboratory demonstrated that TQ has a significant inhibitory effect on the migration and invasion of triple negative breast cancer cells. Methods: To find the new target genes for the inhibition of migration and invasion of breast cancer cells by TQ, RNA-sequencing (RNA-seq) was conducted with and without TQ in human breast cancer cell line BT-549 with high invasion and migration characteristics. Quantitative and semi-quantitative RT-PCR was used to further verify the genes regulated by TQ, and then Western Blotting was used to compare the changes of the genes regulated by TQ at the protein level. Finally, the molecular mechanism of TQ inhibiting migration and invasion of human breast cancer cells was investigated by increasing or decreasing the expression of these genes. Results: Eighteen differentially expressed genes, which were closely related to the carcinomas in the experimental group and the control group, were obtained by RNA-seq. HSPA6 gene changed significantly, and showed an up-regulation after adding TQ, which was consistent with the results of RNA-seq. By RT-PCR and Western Blotting from different cell lines (BT549, MCF-7, ZR-75-30, SiHa, Caski), we found that the expression of HSPA6 in the experimental group was higher than that in the control group. The subsequent TQ treatment after knockdown / over-expression will be completed for HSPA6 protein functional effects by TQ. Conclusion: HSPA6 may be a new target gene for TQ to inhibit the migration and invasion of breast cancer cells. The success of this study will provide a new candidate target for clinical treatment of breast cancer. Funding support: National Natural Science Foundation of China (Grant No. 81672887, 81172049) Citation Format: Shiyi Shen, Ting Xiao, Ju Zhou, Chunli Wei, Junjiang Fu. HSPA6 may be a new target by thyraquinone inhibiting migration and invasion of breast cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5259.

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