Jing Chen

Purpose: To investigate the effects of YKT6 on lung cancer proliferation, migration, invasion, and autophagy. Methods: Differential expression analysis, clinical characteristics correlation analysis, Kaplan–Meier survival analysis, and univariate and multivariate Cox regression analyses were performed to explore the expression and clinical significance of YKT6 in lung cancer. The clone formation assay, MTT assay, scratch assay, transwell assay, AO fluorescence staining assay and western blot assay was detect the effect of YKT6 on cell proliferation, migration, invasion and autophagy. YKT6 co-expressed genes were collected by LinkedOmics database and analyzed by GO and KEGG enrichment to explore the role of YKT6 in the regulation of lung cancer pathways. Flow cytometry and western blot experiments were used to detect the cell cycle changes and the expression levels of cell cycle-related proteins in knockdown YKT6 cells. Results: YKT6 was highly expressed in lung cancer tissues, and its expression was correlated with clinical characteristics. The high expression of YKT6 led to a poor prognosis of lung cancer patients. YKT6 affected the proliferation, migration, invasion and autophagy of lung cancer cells. YKT6 impacted the disease progression of lung cancer through cell cycle regulation. The high expression of YKT6 increased the expression of Cyclin A protein and Cyclin D1 protein expression levels, while inhibiting the expression of p21 protein and p27 protein. Conclusions: YKT6 is highly expressed in lung cancer. YKT6 promotes proliferation, migration and invasion, and inhibits autophagy in lung cancer.

Eleutheroside B, also known as syringin, has been shown to have various pharmacological activities such as anti-inflammatory, anti-irradiation and antidepressant, but there are few studies on its anti-cancer activity. Its anti-tumor effect on SMMC-7721 cells has not been revealed. Moreover, whether it induces autophagy is still unclear. Thus, the present study investigated whether Eleutheroside B induces apoptosis, autophagy and cellular motility in SMMC-7721 cells and HeLa cells, and explored the underlying molecular mechanisms. SMMC-7721 cells and HeLa cells treated with Eleutheroside B and cell viability measured by MTT assay and trypan blue dye exclusion assay. Apoptosis checked by flow cytometry combined, fluorescent staining. Apoptotic signal proteins and autophagy proteins were checked by Western blot. This study showed that Eleutheroside B inhibited the cell proliferation and blocked cell cycle, migration and invasion as well. Moreover, Eleutheroside B induced apoptosis in SMMC-7721 cells and HeLa cells. It upregulated Bax expression, while simultaneously decreasing Bcl-2 expression. Further elucidation of the mechanism revealed that Eleutheroside B induced mitochondrial dysfunction, with mitochondrial membrane potential collapse and cytochrome c release, suggesting that Eleutheroside B induced apoptosis by triggering mitochondrial pathway. Most importantly, Eleutheroside B could induce autophagy in SMMC-7721 cells and HeLa cells. Taken together, these results suggested Eleutheroside B is a potential therapeutic candidate for HCC and Human cervical cancer.

Background: In a previous study, unrecognized role of gMYL6 in the up-regulation of human NK cells' development and cytotoxicity was reported. Objective: To further elucidate the mechanism of action of small fragments recombinant of gMYL6 enhancing the NK cells activity. Methods: Mononuclear cells were isolated from umbilical cord blood (UCB) by density-gradient centrifugation and NK cells were propagated and cultured. The small peptides from the gMYL6, with ability to enhance the cytotoxicity of NK cells were screened by CCK-8 method and one of the most powerful peptides was identified for the next study. Flow cytometry were used to explore the proliferation and apoptosis of K562 cells, as well as the cell cycle arrest. The apoptosis of target cells was observed by AO/EB fluorescence staining, and the value of apoptosis was detected by flow cytometry. The method of protein imprinting was also used to explore the pathway of small peptides to enhance the NK cells activity. On the other hand, Real-time Quantitative PCR Detecting System was used to verify the mechanism of K562cell suppression. Results: Small D peptide significantly increased NK cells cytotoxicity and induced both cell cycle arrest at G2/M and apoptosis of K562 cell. Conclusion: Small D could be a novel promising peptide against cancers since it showed the capacity to promote the cord blood-derived NK cells' cytotoxicity.

Siomycin A is a type of thiopeptide antibiotic that is isolated from the fermentation products of an endophytic actinomycin, which is derived from the medicinal plant Acanthopanax senticosus. The present study investigated whether siomycin A has antitumor effects in vitro on a variety of cell lines. A Cell Counting Kit‑8 assay was performed to detect the effects of siomycin A on cell viability; morphological changes in the MiaPaCa‑2 cell line were analyzed using an inverted phase contrast microscope. A Transwell migration assay was applied to detect cell migration ability. The cytoskeleton was observed by laser confocal microscopy, and apoptosis was detected using flow cytometry. A western blot assay was used to detect the expression of matrix metalloproteinase (MMP)‑2, MMP‑9 and α‑tubulin. The results revealed that siomycin A inhibited the proliferation of human tumor cell lines of different origins. As the concentration of siomycin A increased, the cell density decreased gradually and cells exhibited a morphological change from spindle to spherical shape. Furthermore, 24 h after administration, the cell migration ability was inhibited. The cytoskeleton complexity and morphological changes were increased after administration of siomycin A. The percentage of apoptotic cells was significantly increased and the expression levels of MMP‑2, MMP‑9 and α‑tubulin were downregulated by siomycin A. Therefore, siomycin A was determined to effectively inhibit the proliferative ability of a variety of human tumor cell lines. Siomycin A was also determined to affect the cytoskeleton of tumor cells by downregulating the expression of α‑tubulin protein.

Mutations of the Ras oncogene are frequently detected in human cancers. Among Ras‐mediated tumorigenesis, Kras‐driven cancers are the most dominant mutation types. Here, we investigated molecular markers related to the Kras mutation, which is involved in energy metabolism in Kras mutant‐driven cancer. We first generated a knock‐in Kras^G12D cell line as a model. The genotype and phenotype of the Kras ^G12D‐driven cells were first confirmed. Dramatically elevated metabolite characterization was observed in Kras ^G12D‐driven cells compared with wild‐type cells. Analysis of mitochondrial metabolite‐related genes showed that two of the 84 genes in Kras ^G12D‐driven cells differed from control cells by at least twofold. The messenger RNA and protein levels of ATP6V0D2 were significantly upregulated in Kras ^G12D‐driven cells. Knockdown of ATP6V0D2 expression inhibited motility and invasion but did not affect the proliferation of Kras ^G12D‐driven cells. We further investigated ATP6V0D2 expression in tumor tissue microarrays. ATP6V0D2 overexpression was observed in most carcinoma tissues, such as melanoma, pancreas, and kidney. Thus, we suggest that ATP6V0D2, as one of the V‐ATPase (vacuolar‐type H ⁺‐ATPase) subunit isoforms, may be a potential therapeutic target for Kras mutation cancer.

Apoptosis induction and differentiation of promyelocytic leukemic cells into mature cells are major strategies for the drug-based treatment of leukemia. Lidamycin (LDM) which is a member of the enediyne antibiotic family exhibits extreme cytotoxicity. In the present study, the induction of apoptosis and differentiation in human chronic myeloid leukemia K562 cells by low concentrations of lidamycin were investigated. K562 cells were treated with lidamycin at various concentrations for 48 h, and accumulated in the metaphase as determined in previous experiments. Cell viability was determined using a Cell Counting Kit-8 (CCK-8) assay and the IC50 value of lidamycin was 0.1 +/- 3.2 nM. Induction of apoptosis was investigated morphologically by acridine orange/ethidium bromide (AO/EtBr) staining. Growth inhibition and apoptosis induction were observed in cells treated with low concentrations of lidamycin. In addition, western blot analysis revealed that treatment of the K562 cells with lidamycin at low concentrations upregulated the expression of caspase-8 and caspase-3. The induction of differentiation in human chronic myeloid leukemia K562 cells by lidamycin at low concentrations was also investigated. The nitroblue tetrazolium reduction ability of K562 cells was increased following treatment with lidamycin. Low concentrations of lidamycin triggered erythroid differentiation among K562 cells, indicated by morphological changes, increased hemoglobin content, and the expression of cell surface antigens such as CD71. Additionally the expression of GATA-binding factor 1 (GATA-1) protein in low concentration lidamycin-treated K562 cells was increased. The results of the present study suggest that a low-concentration lidamycin exerts effects on apoptosis and erythroid differentiation induction by increasing the expression of caspases and GATA-1 protein. Lidamycin may serve a positive role in relevant targeted chemotherapy and may represent a potential candidate for chronic myelogenous leukemia differentiation-inducing treatment.