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  1. Article ; Online: G9a-targeted chaetocin induces pyroptosis of gastric cancer cells

    Mian-Qing Huang / Gui-Lan Tao / Li-Fang Han / Shu-Hong Tian / Peng Zhou

    Asian Pacific Journal of Tropical Biomedicine, Vol 13, Iss 6, Pp 268-

    2023  Volume 276

    Abstract: Objective: To evaluate the effect of chaetocin on pyroptosis of gastric cancer cells and its underlying mechanisms. Methods: The proliferation of gastric cancer cells was detected by trypan blue staining. Flow cytometry and Hoechst/propidium iodide ... ...

    Abstract Objective: To evaluate the effect of chaetocin on pyroptosis of gastric cancer cells and its underlying mechanisms. Methods: The proliferation of gastric cancer cells was detected by trypan blue staining. Flow cytometry and Hoechst/propidium iodide double staining were used to detect apoptosis and pyroptosis. Cellular ultrastructure was observed by transmission electron microscopy. The levels of p-mixed lineage kinase domain-like (MLKL), gasdermin-D (GSDMD), gasdermin E (GSDME), N-GSDMD, and N-GSDME proteins were detected by Western blotting. In addition, lactate dehydrogenase (LDH) release assay was used to verify pyroptosis induced by chaetocin, and caspase 3 inhibition test and siRNA interference test were conducted to investigate pyroptosis mechanisms. Results: Chaetocin at concentrations of 200 nmol/L to 600 nmol/L inhibited the proliferation of AGS, HGC27, MKN28, and SGC7901 gastric cancer cells in a dose-dependent and time-dependent manner by inducing apoptosis and pyroptosis. Significant ultrastructure changes, such as chromatin condensation, vacuolization, disrupted mitochondrial cristae, and increased nuclear occupancy, were observed after treatment with chaetocin in SGC7901 cells. Chaetocin at a concentration of 400 nmol/L significantly increased the number of pyroptotic cells, LDH release, and the ratio of N-GSDME/ GSDME (P<0.01), which were reversed by Z-DEVD-FMK. In addition, chaetocin did not affect the expression of GSDMD. G9a silencing abolished the effect of chaetocin on the expression levels of GSDME and N-GSDME and LDH release (P>0.05). Conclusions: In addition to inducing apoptosis, chaetocin inhibits gastric cancer cells by inducing pyroptosis via the caspase 3/GSDME pathway. G9a was the target of chaetocin to induce pyroptosis of gastric cancer cells.
    Keywords chaetocin ; gastric cancer ; pyroptosis ; g9a ; gsdme ; Arctic medicine. Tropical medicine ; RC955-962 ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Wolters Kluwer Medknow Publications
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Feng-liao-chang-wei-kang is synergistic with 5-fluorouracil in inhibiting proliferation of colorectal cancer

    Pan-Li Ni / Shu-Hong Tian / Zhao-Xin Yang / Jun-Qing Zhang / Fan Yang / Li-Fan Zhong / Lian-Fang Gan / Mian-Qing Huang / Ling Huang

    Asian Pacific Journal of Tropical Medicine, Vol 12, Iss 14, Pp 41-

    2019  Volume 53

    Abstract: Objective: To explore the effect of Feng-liao-chang-wei-kang (FLCWK) on acute and chronic gastroenteritis, synergistic effect on the growth inhibitory effect with 5-fluorouracil (5-FU) on colorectal cancer and its underlying mechanisms. Methods: In the ... ...

    Abstract Objective: To explore the effect of Feng-liao-chang-wei-kang (FLCWK) on acute and chronic gastroenteritis, synergistic effect on the growth inhibitory effect with 5-fluorouracil (5-FU) on colorectal cancer and its underlying mechanisms. Methods: In the in vitro study, HT-29 cells were divided into 5-FU alone, FLCWK alone and coadministration groups. The MTT assay was used to analyze the proliferation of HT-29 cells at 24 h. Flow cytometry was used to observe the apoptosis, cycle of colorectal cancer HT-29 cells at 24 h. In the in vivo experiment, The subcutaneous transplantation tumor model of colorectal cancer HT-29-Luc was established with nude mice. All mice were randomly divided into 5-FU alone, FLCWK alone and coadministration groups according to body weight. During administration, the Interactive Video Information System small animal live imaging system was used to monitor the growth of subcutaneous transplantation in nude mice. The model of colitis-associated colorectal cancer (CACC) was established with BALB/c mice. BALB/c mice were randomly divided into the normal control group, the model control group, and the FLCWK group. At the end of the administration, the pathological status was detected by HE staining. Cell apoptosis of tumor tissue tumor and colon tissues were observed by TUNEL staining and TUNEL green fluorescence. The protein expression of Caspase 3, p-STAT3, Bcl-2, Bax and P-gp in tumor tissues tumor and colon tissues were tested by using immunohistochemical assay. Results: FLCWK and 5-FU coadministration suppressed HT-29 cell viability and induced S phase arrest and apoptosis compared to treatment with 5-FU alone. Furthermore, compared to treatment with 5-FU alone, coadministration of FLCWK and 5-FU obviously reduced tumor volume and weight and induced apoptosis through decreasing p-STAT3 and P-gp and increasing Caspase 3 protein expression in a murine xenograft tumor model. Moreover, the result revealed decreased number and size of tumors following FLCWK protective administration, downregulated p-STAT3 and Bcl-2 levels and upregulated Bax and Caspase 3 expression in mice with CACC. Conclusions: FLCWK has synergistic effects with 5-FU on colorectal cancer by suppressing the STAT3 pathway and downregulating P-gp expression. Furthermore, FLCWK administration suppresses CACC tumorigenesis by inhibiting the STAT3 pathway.
    Keywords colorectal cancer ; flcwk ; 5-fluorouracil ; synergistic effect ; colitis-associated colorectal cancer ; Arctic medicine. Tropical medicine ; RC955-962
    Subject code 610
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Wolters Kluwer Medknow Publications
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Recombinant human calcineurin B inhibits orthotopic hepatocellular carcinoma xenograt growth in mice by promoting apoptosis

    Xiao-Dian Zhang / Zhi-Hui He / Li-Ping Zheng / Guo-Hui Yi / Min-Ge Lin / Li-Zhen Fu / Shu-Hong Tian / Hong-Hai Li / Yan-Da Lu / Shen-Hong Gu / Shao-Jiang Zheng

    Asian Pacific Journal of Tropical Medicine, Vol 12, Iss 14, Pp 32-

    2019  Volume 40

    Abstract: Objective: To explore the effects of recombinant human calcineurin B (rhCNB) on hepatocellular carcinoma in mice. Methods: An in vivo mouse model with hepatocellular carcinoma was established, and the mice were randomized into the rhCNB, positive control ...

    Abstract Objective: To explore the effects of recombinant human calcineurin B (rhCNB) on hepatocellular carcinoma in mice. Methods: An in vivo mouse model with hepatocellular carcinoma was established, and the mice were randomized into the rhCNB, positive control and vehicle treatments groups. Tumor growth was assessed via bioluminescence using a small animal imaging system. Relative tumor proliferation rate and tumor growth inhibition were calculated. The expression of p53 and caspase-9 proteins in tumors were detected by immunohistochemistry. In vitro, flow cytometry was used to quantify the cell-cycle stages and rate of apoptosis. Western blotting and quantitative real-time PCR assays were used to evaluate the effects of rhCNB on protein and gene expression of CDK1, cyclin B1, p53 and caspase-9. Results: rhCNB at the higher dose significantly reduced tumor growth in vivo and caused tumor cell apoptosis in vitro. The rhCNB at the higher dose was as effective as cisplatin, and was safer. Conclusions: rhCNB has potent pro-apoptotic effects on tumor cells in vivo and in vitro and is well tolerated in vivo.
    Keywords mice ; apoptosis ; calcineurin ; cell cycle ; hepatocellular carcinoma ; Arctic medicine. Tropical medicine ; RC955-962
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Wolters Kluwer Medknow Publications
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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