स्तन कैंसर के विकास में जिनसेनोसाइड Rh2 के कार्य में तल्लीन
1. परिचय
According to the 2020 report ofWorld Health Organization (WHO), there are approximately 2.3 million cases with breast cancer worldwide. Breast cancer has emerged as one of the most malignant tumor in females withsignificantincidence rate. Although great progress has made in improving the cure rate of early-stage breast cancer in recent years, advanced breast cancer is still hard to be cured.How to reduce the risk of recurrenceand metastasis of early-stage breast cancer as well as prolong the survival of patients with advanced breast cancer is still a challenge in the clinical treatment of breast cancer. Notably, g参皂苷 Rh2 (GRh2) exerts prominent impacts on retarding the progression of breast cancer via strengthening the immune surveillance of natural killer (NK) cells, a kind of cytotoxic innate lymphocytes critical for tumor immune response.
2. The repressive role of GRh2 in the progression of breast cancer
GRh2hinders the growth, proliferation and metastasis of breast cancer. Simply put, the body weightand tumor volume的 model mice are markedly reduced post treatment of GRh2 (10 mg/kg and 20 mg/kg). In addition, the proliferating rate of breast cancer cells is repressed by GRh2 in a dose-dependent manner (5, 10 and 20 mg/kg). Upon the treatment of GRh2 (20 mg/kg), the loss of lung capacity is obviously reduced and the lung metastases formed by MDA-MB-231 tumor cells are strikingly mitigated as well, with no apparent liver metastatic nodules.3. The enhanced killing effect of NK cells on breast cancer cells followingGRh2 treatment
GRh2 exerts remarkable effects on retarding the progression of breast cancer via improving the killing ability of NK92MI cells. In a nutshell,themRNA expression levels of killing mediators perforin and IFN-γ in NK92MI cell-breast cancer cell co-culture system are explicitly upregulated post GRh2 treatment. Strikingly, the reduced lung metastasis of breast cancer byGRh2is almostcounteracted upon the depletion of NK cells. Relative tothat ofthe vehicle control, the amount of CD107a, a degranulation marker of NK cells, is overtly elevated in the presence of GRh2 (20 mg/kg), verifying the enhanced killing activity of NK cells on breast cancer.4. The underlying molecular mechanism ofGRh2on potentiating the NK cell activity against breast cancer
Breast cancer cells reduce the recognition by NKG2D through proteolytic shedding MICA mediated by ERp5 to escape NK cell surveillance. GRh2 interferes with the formation of soluble MICA (sMICA) bysuppressing the expression of ERp5 to increase the contents of killing mediators from NK cells, thereby exerting striking effects on fighting against breast cancer.
5. Conclusion
GRh2potentiates the cytotoxic effect of NK cells andenhances the immune surveillance function of NK cells to fight against breast cancer, which may be a potent drug candidate for the prevention and treatment of breast cancer.参考文献
[1] Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660
[2] Yang C, Qian C, Zheng W, et al. Ginsenoside Rh2 enhances immune surveillance of natural killer (NK) cells via inhibition of ERp5 in breast cancer. Phytomedicine. 2024;123:155180. doi:10.1016/j.phymed.2023.155180
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