The inhibitory effect and molecular mechanism of delphindin on HER-2 positive breast cancer / 天津医药

@#Objective To investigate the inhibitory effect and molecular mechanism of delphinidin (Dp) on HER-2 positive breast cancer. Methods The HER-2 positive breast cancer cells (MDA-MB-453 and BT-474) were treated with different concentrations of delphinidin (10，20，40，80 and 160 μmol/L) for 48 hours. The same concentration of DMSO was used as the solvent control. CCK-8 method was used to measure the effect of Dp on cell activity, and half maximal inhibitory concentration (IC50) was calculated to determine the concentration of subsequent experiments. The cells were treated with different concentrations of Dp (20, 40 and 80 μmol/L) for 48 hours. HE staining was used to observe the cell morphological changes. Flow cytometry was used to analyze the cell cycle. Cell apoptosis rate was detected by TUNEL assay. The phosphorylation levels of NF - κB signaling pathway related proteins were determined by Western blot assay. Results Delphinidin inhibited the proliferation of MDA-MB-453 and BT-474 in the concentration ranges of 10，20，40，80 and 160 μmol/L (IC50: 41.02 and 60.97 μmol/L). In the concentrations of 20，40 and 80 μmol/L, compared with the control group, it was found that some cells were detached, floated and lysed, and the cell volume was decreased, the proportion of cells in G2/ M phase and the apoptosis rate were increased in DP treatment groups. Compared with the control group, the expression levels of p-NF-κB/p65, p-IκBα, p-IKKα/β and p-PKCα were significantly decreased in the 40 and 80 μmol/L Dp treatment groups, while the expression levels of IκBα, IKKα, IKKβ and PKCα were increased in the Dp treatment groups (P＜0.05). Conclusion Delphinine can inhibit the proliferation of breast cancer cells by blocking the NF-κB signaling pathway and inducing the G2/M cycle arrest and apoptosis of MDA-MB-453 and BT-474 cells. Key words：receptor, epidermal growth factor; antineoplastic agents, phytogenic; breast neoplasms; cell cycle; delphinidin;HER-2 positive breast cancer; NF-κB signaling pathway

Inhibitory effect of sanguinarine on growth of xenograft tumors of gastric cancer GTL-16 cells in nude mice and its related mechanism / 肿瘤

Objective: To investigate the antitumor effect of sanguinarine (SAN) in vivo and its possible mechanism. Methods: The tumor-bearing BALB/c male nude mouse models were established by subcutaneous inoculation of gastric cancer GTL-1 6 cells. The mouse models were divided into three groups [14 mice in each group were intragastrically administered with 0.9% NaCl solution (as the control group), 2.5 mg/kg SAN and 5.0 mg/kg SAN every other day for 7 times, respectively]. The general status of the mice was observed, and the tumor volume was measured. After 28 days, the mice were sacrificed, then the tumor volume and weight were recorded. The histopathologic examination of tumor tissues was performed using hematoxylin-eosin (HE) staining. Then the protein expression of epidermal growth factor receptor (EGFR) in tumor tissues was detected by Western blotting. Results: As compared with the control group, the tumors grew slowly in SAN treatment groups. At autopsy, the volume and weight of tumors in SAN treatment groups were all smaller than those in the control group (P < 0.01), and the tumor volume and weight were smallest in 5.0 mg/kg SAN group (P < 0.01). The result of histopathologic examination revealed that SAN treatment could reduce the accumulation of tumor cells and epidermal invasion of tumor cells. The expression levels of EGFR were significantly lower in SAN treatment groups than that in the control group (P < 0.05). Conclusion: SAN inhibits the growth of tumor in nude mice inoculated with gastric cancer GTL-16 cells, and which may be related to the downregulation of EGFR expression.

Antitumor effect of Ganoderma(Lingzhi) mediated by immunological mechanism and its clinical application / 中国药理学与毒理学杂志

The anti-tumor effect of Ganoderma(Lingzhi) is closely related to immunoregulation. Based on our research and other references,this article discussed the antitumor effect of Ganoderma mediated by immunological mechanism, including promoting the function of mononuclear-macro?phages,and natural killers,promoting maturation and differentiation of dendritic cells,increasing its antigen presentation,activating lymphocytes and increasing cytotoxicity of cytotoxin T lymphocyte, promoting production of cytokines,inhibiting tumor escape from immune surveillance. Also, clinical studies with immunological indexes were reviewed.

Plant extract anti-cancer research progress / 国际肿瘤学杂志

Plant extracts are kinds of important anticancer drugs.Anticancer drugs research has focused on several important plant extracts such as resveratrol,ricin,epigallocatechin-3-gallate,oridonin,juglone,quercetin,matrine,nordihydroguaiaretic acid.In vitro and in vivo studies have shown that their antitumor mechanisms including induction of apoptosis,cytotoxicity,induced redifferentiation,antiangiogesis,antiinvasion and anti-metastasis.Plant extracts have multi-link and multi-target.Part of them have been used in preclinical studies.In-depth study of the anti-tumor mechanisms of plant extracts on cancer treatment is important,and the full mechanism needs further study.

Anticancer effect of lupeol, a triterpene / 国际肿瘤学杂志

Lupeol,a triterpene,is found in various edible and medicinal plants.Lupeol has been shown to exhibit strong anti-inflammatory,anti-arthritic,gene mutation prevention and anti-malarial effect.Recently,it is found that lupeol is the main active ingredients of inhibiting the growth of a several kinds of cancers and carcinomas in some antineoplastic plants.Lupeol has antineoplastic effect.

Study on the mechanism of gambogenic acid-induced apoptosis of human colon cancer HCT116 cells / 肿瘤

Objective: To investigate the pro-apoptotic effect of gambogenic acid (GNA) on human colonic carcinoma HCT116 cells, and to explore the possible molecular mechanism. Methods: MTT assay was performed to detect proliferation inhibition effect of GNA on HCT116 cells. After staining with DAPI, the pro-apoptotic effect of GNA on HCT116 cells was observed under a fluorescence microscope. The changes in cell cycle distribution of HCT116 cells induced by GNA were examined by FCM. The expressions of cyclin D1, cyclin E, P21, P27 and poly (ADP-ribose) polymerase (PARP) proteins in HCT116 cells were detected by Western blotting. Results: GNA exerted an significant inhibitory effect on HCT116 cell proliferation in a time-and dose-dependent manner, and it could induce the typical nuclear apoptotic morphology. Under a fluorescence microscope, DAPI staining results showed that GNA could obviously induce the apoptosis of HCT116 cells. FCM showed that GNA could significantly increase the percentage of cells at G0/G1 phase, whereas obviously decrease the percentage of cells at S phase, which indicated that the cell cycle was arrested at G 0/G1 phase. Western blotting analysis showed that GNA could efficiently down-regulate the expression levels of cyclin D1 and cyclin E proteins, whereas up-regulate the expression levels of P21 and P27 proteins, and also promote the cleavage of PARP. Conclusion: GNA can induce the cell cycle arrest at G0/G1 phase by down-regulating the expression levels of cyclin D1 and cyclin E, and up-regulating the expression levels of P21 and P27. Therefore, GNA can efficiently promote the cell proliferation inhibition and the apoptosis of HCT116 cells. Copyright© 2011 by TUMOR.

Inhibition of cell proliferation by a resveratrol analog in human pancreatic and breast cancer cells

Resveratrol has been reported to possess cancer preventive properties. In this study, we analyzed anti-tumor activity of a newly synthesized resveratrol analog, cis-3,4',5-trimethoxy-3'-hydroxystilbene (hereafter called 11b) towards breast and pancreatic cancer cell lines. 11b treatments reduced the proliferation of human pancreatic and breast cancer cells, arrested cells in the G2/M phase, and increased the percentage of cells in the subG1/G0 fraction. The 11b treatments also increased the total levels of mitotic checkpoint proteins such as BubR1, Aurora B, Cyclin B, and phosphorylated histone H3. Mechanistically, 11b blocks microtubule polymerization in vitro and it disturbed microtubule networks in both pancreatic and breast cancer cell lines. Computational modeling of the 11b-tubulin interaction indicates that the dimethoxyphenyl group of 11b can bind to the colchicine binding site of tubulin. Our studies show that the 11b treatment effects occur at lower concentrations than similar effects associated with resveratrol treatments and that microtubules may be the primary target for the observed effects of 11b. These studies suggest that 11b should be further examined as a potentially potent clinical chemotherapeutic agent for treating pancreatic and breast cancer patients.

Experimental observation of Hep-2 cell cycle progression by elemene combined with heperthermia / 中国耳鼻咽喉头颈外科

OBJECTIVE To observe the inhibition of elemene combined with heperthermia on the cultured Hep-2 cell line(human laryngeal cancer cell line).METHODS MTT was applied to detect Hep-2 cell proliferation inhibition rate.Flow cytometry was applied to detect cell cycle and apoptosis rate of Hep-2 cells and electronic microscope was applied to detect subcellular changing of Hep-2 cells.RESULTS The inhibition rates were 28.8%,25.7% and 47.1% in elemene group,heperthermia group and elemene combined with heperthermia group respectively.The result of elemene combined with byperthermia group was the most effective.Elemene combined with hyperthermia can significantly increase the proliferation inhibition rate and the apoptosis rate of the Hep-2 cell.The cell cycle progression can be changed obviously.The number of G1 phase cells increased,the number of S phase cells decreased while the cells in G2/M phase increased relatively.At the subcellular level,the swelled mitochondrial,the chromatin agglutination edge trended and apoptotic bodies were observed under electronic microscope.CONCLUSION Elemene combined with hyperthermia can keep Hep-2 from proliferation and inhibit the changing from G1 phase to S phase,so the apoptosis rate can be induced.