Ginsenoside Rg5 induces NSCLC cell apoptosis and autophagy through PI3K/Akt/mTOR signaling pathway.

OBJECTIVE: Ginsenoside Rg5 (Rg5) is a minor ginsenoside of ginseng and has a strong anti-tumor potential. This study focused on deciphering the function of Rg5 in non-small cell lung cancer (NSCLC) and investigating its related mechanism. METHODS: After treating human NSCLC cell lines (H1650 and A549) and bronchial epithelial cells (BEAS-2B) with increasing concentration of Rg5, cell viability was examined using methyl thiazolyl tetrazolium (MTT) assay. NSCLC cell proliferation and apoptosis were evaluated by colony formation assay and flow cytometry, respectively. The levels of proteins associated with cell cycle progression, cell apoptosis, and autophagy as well as the key markers in the PI3K/Akt/mTOR pathway were measured using western blot. A xenograft nude mouse model was established to explore the function of Rg5 in vivo. RESULTS: NSCLC cell viability was dose- and time-dependently suppressed after Rg5 treatment. Rg5 restrained NSCLC cell proliferation by inducing G2/M phase arrest via regulation of cell cycle-related genes including p21, cyclin B1, and Cdc2. Additionally, Rg5 promoted caspase-dependent apoptosis in NSCLC cells by regulating the intrinsic mitochondrial signaling pathway. Rg5 induced autophagy via the regulation of autophagy-related proteins. The in vivo experiments revealed the inhibitory impact of Rg5 on xenograft growth. Rg5 also inactivated the PI3K/Akt/mTOR signaling pathway in NSCLC cells and mouse tumors. CONCLUSION: Rg5 induced autophagy and caspase-dependent apoptosis in NSCLC cells by inhibiting the PI3K/Akt/mTOR signaling pathway, suggesting that Rg5 might become a promising and novel anti-tumor agent for the clinical treatment of NSCLC patients.

Genome-Wide Identification and Analysis of the WNK Kinase Gene Family in Upland Cotton.

With-No-Lysine (WNK) kinases are a subfamily of serine/threonine protein kinases. WNKs are involved in plant abiotic stress response and circadian rhythms. However, members of the WNK subfamily and their responses to abiotic and biotic stresses in Gossypium hirsutum have not been reported. In this study, 26 GhWNKs were identified in G. hirsutum. The gene structure, conserved motifs, and upstream open reading frames (uORFs) of GhWNKs were identified. Moreover, GhWNKs regulation is predicted to be regulated by cis-acting elements, such as ABA responsive element (ABRE), MBS, and MYC. Furthermore, transcription factors including MIKC_MADS, C2H2, TALE, bZIP, Dof, MYB, bHLH, and HD-ZIP are projected to play a regulatory role in GhWNKs. The expression patterns of GhWNKs under normal conditions and biotic and abiotic stresses were evaluated, and their expression was found to vary. The expression patterns of several GhWNKs were induced by infiltration with Verticillium dahliae, suggesting that several GhWNKs may play important roles in the response of cotton to V. dahliae. Interestingly, a homoeologous expression bias within the GhWNKs was uncovered in upland cotton. Homoeologous expression bias within GhWNKs provides a framework to assist researchers and breeders in developing strategies to improve cotton traits by manipulating individual or multiple homeologs.

Targeting of the tumor immune microenvironment by metformin.

Stimulating antitumor immunity is an attractive idea for suppressing tumors. CD4 + and CD8 + T cells as well as natural killer cells (NK) are the primary antitumor immune cells in the tumor microenvironment (TME). In contrast to these cells, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), cancer-associated fibroblasts (CAFs), and tumor-associated macrophages (TAMs) release several molecules to suppress antitumor immunity and stimulate cancer cell invasion and proliferation. Adjuvant treatment with certain nontoxic agents is interesting to boost antitumor immunity. Metformin, which is known as an antidiabetes drug, can modulate both antitumor and protumor immune cells within TME. It has the ability to induce the proliferation of CD8 + T lymphocytes and NK cells. On the other hand, metformin attenuates polarization toward TAMs, CAFs, and Tregs. Metformin also may stimulate the antitumor activity of immune system cells, while it interrupts the positive cross-talk and interactions between immunosuppressive cells and cancer cells. The purpose of this review is to explain the basic mechanisms for the interactions and communications between immunosuppressive, anti-tumoral, and cancer cells within TME. Next, we discuss the modulating effects of metformin on various cells and secretions in TME.