"Shihu" promote T-cell immunity against breast cancer through bioactive constituent THMB enhancing JAK3-STAT1 signal.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium, commonly known as "Shihu", are the well-known Chinese traditional medicine with the ability of strengthening "Yin", tonify five viscera, lighten the body, prolong life span that were involved in immunity regulation. However, their T-cell-mediated cellular immune function was kept unknown.

AIM OF THE STUDY: To investigate its T-cell-mediated cellular immune function, and reveal bioactive constituents and mechanism.

MATERIALS AND

METHODS

The eliminating of mutant cells (cancer cells) by T-cell-mediated cellular immune was used to evaluate T-cell immunomodulation function through the non-traditional cytotoxicity T-cell immunomodulatory anti-tumor model combination with bioactivity-guided isolation. The LDH killing and ELISA analysis were used to examine killing efficacy and cytokines. The vaccine adjuvant model of mouse breast cancer was used to evaluate T-cell immunomodulation efficacy in vivo. The proteome and phosphoproteome analysis were used to mechanism research combined with blocking rescue analysis.

RESULTS

"Shihu" fraction (YD198-6) showed the T-cell immunomodulation killing cancer cells bioactivity among the seven extracts, and fifteen known compounds were identified by bioactivity-guided isolation, which revealed the compound 3,4',5-trihydroxy-3'-methoxybiphenyl (THMB) was a better bioactive constituent. Further mechanism research suggested THMB regulated T-cell against multiple tumor cells major through enhancing JAK3-STAT1 signal to upregulate granzyme B, perforin, IL-1β. Moreover, in mice TNBC model, the primary tumor growth was significantly inhibited about 62%, and lung metastasis was reduced about 51% accompanied with significantly improving overall survival (54 days vs 37 days, p < 0.05).

CONCLUSION

These results demonstrated that "Shihu" could enhance T-cell mediated cellular immune function to protect health, and revealed its bioactive constituent and mechanism.