open access: Ganoderma tsugae Extract Inhibits Growth of HER2-Overexpressing Cancer Cells via Modulation of HER2/PI3K/Akt Signaling Pathway

open access

In conclusion, we provide a schematic presentation of possible molecular mechanisms in vitro and in vivo for the inhibitory effects of GTE on the proliferation of HER2-overexpressing cancer cells (Figure 6). Our results indicate that GTE induces G1 cell cycle arrest via regulation of the HER2/PI3K/Akt signaling pathway, thereby leading to a reduction in the growth of cancer cells overexpressing HER2. Our data also demonstrate that the depletion of HER2 protein by GTE involves an inhibition in the transcriptional activity of the HER2 gene and an increase in the proteasome-dependent degradation of the HER2 protein. In addition, we have also shown that a combination of GTE with anticancer drugs (e.g., taxol, cisplatin, and doxorubicin) exerts synergistic growth-inhibitory effect on HER2-overexpressing cancer cells. Taken together, our findings suggest that GTE may be a useful and effective adjuvant therapeutic agent for the treatment of cancers that highly express HER2.