[Ginsenoside Rg3 Regulates Cisplatin Resistance in Gastric Cancer by Wnt/ß-catenin Signaling Pathway].

Objective To investigate the inhibitory effect of ginsenoside Rg3 combined with cisplatin (DDP) on DDP-resistant cell line SGC-7901/DDP and their molecular mechanism.Methods SGC-7901/DDP cells were divided into four groups including a control group,a ginsenoside Rg3 (40 µg/ml) treatment group,a DDP (1.40 µg/ml) treatment group,and a drug combination treatment group.The proliferation ability of SGC-7901/DDP cells was detected by MTT,EdU,and colony formation assays.The apoptosis ability of SGC-7901/DDP cell was detected by flow cytometry and Hoechst 33342 staining.The protein levels of apoptosis-related markers were detected by Western blotting.The migration ability of SGC-7901/DDP cells was detected by wound healing and Transwell assays.The expression levels of proteins in epithelial-mesenchymal transformation (EMT) and Wnt/ß-catenin signaling pathway were determined by Western blotting and immunofluorescence staining.Results Compared with the ginsenoside Rg3 or the DDP treatment groups,the drug combination treatment group inhibited the proliferation (t=8.062,P=0.001;t=7.090,P=0.002),colony formation (t=8.062,P=0.001;t=6.144,P=0.004),and migration (t=7.424,P=0.002;t=4.317,P=0.013),and promoted the apoptosis (t=5.530,P=0.031;t=6.036,P=0.026) of SGC-7901/DDP cells.Compared with the ginsenoside Rg3 and the DDP treatment groups,the drug combination treatment group down-regulated the expression levels of EMT-associated proteins including vimentin (t=24.450,P<0.001;t=14.750,P<0.001),Snail (t=29.640,P<0.001;t=70.700,P<0.001),Slug (t=89.230,P<0.001;t=87.360,P<0.001),matrix metalloproteinase (MMP) 2 (t=84.540,P<0.001;t=67.120,P<0.001),and MMP9 (t=19.010,P<0.001;t=10.890,P<0.001),as well as those of Wnt/ß-catenin signaling pathway related proteins including Wnt (t=35.480,P<0.001;t=14.670,P<0.001),ß-catenin (t=155.800,P<0.001;t=118.100,P<0.001),C-myc (t=20.870,P<0.001;t=3.334,P=0.029),and cyclin D1 (t=5.007,P=0.008;t=8.347,P=0.001).Meanwhile,it up-regulated the expression of epithelial cells including E-cadherin (t=36.450,P<0.001;t=33.810,P<0.001) and ZO-1 (t=37.060,P<0.001;t=37.030,P<0.001).Conclusion Ginsenoside Rg3 enhanced the sensitivity of SGC-7901/DDP cells to DDP by inhibiting the activity of Wnt/ß-catenin signaling pathway.

Pathological analysis and surgical modalities selection of cT1N0M0 solitary papillary thyroid carcinoma in the isthmus.

BACKGROUND: prognosis, identify clinicopathological characteristics, and determine optimal modalities for cT1N0M0 solitary papillary thyroid carcinoma in the isthmus (PTCI). METHODS: The clinical data of 124 patients with cT1N0M0 solitary PTCI from 3 medical centers were analyzed retrospectively. Of these, 32 participants had undergone total thyroidectomy plus unilateral central neck dissection, 36 had received total thyroidectomy plus bilateral central neck dissection, 24 had less-than-total thyroidectomy plus unilateral central neck dissection, and 32 had less-than-total thyroidectomy plus bilateral central neck dissection. We compared the effects of different surgical modalities and clinicopathological characteristics on the prognosis of cT1N0M0 solitary PTCI. RESULTS: There was no significant difference in postoperative recurrence-free survival between participants who received different extents of central region lymph node dissection and thyroidectomies (P>0.05). Temporary hypocalcemia occurred in participants who underwent total thyroidectomy plus bilateral central neck dissection [chi-square (χ2) =7.87, P=0.005]. Tumors with primary lesions ≥0.55 cm were prone to have central lymph node metastasis [95% confidence interval (CI): 0.51 to 0.71, P=0.047]. Multiple logistic analysis suggested that age over 55 years [odds ratio (OR) =11.90, 95% CI: 1.36 to 104.03, P=0.025], tumor size greater than 0.55 cm (OR =4.16, 95% CI: 1.28 to 13.52, P=0.018), and absence of nodular goiter (OR =2.57, 95% CI: 1.05 to 6.32, P=0.04) were risk factors for central lymph node metastasis of patients with cT1N0M0 solitary PTCI. CONCLUSIONS: Less-than-total thyroidectomy is recommended for patients with cT1N0M0 solitary PTCI. Central lymph node dissection is recommended for patients who are prone to have central occult lymph node metastases with tumor size ≥55 cm, older than 55 years, and without nodular goiter.

The 6q25.1 rs2046210 polymorphism is associated with an elevated susceptibility to breast cancer: A meta-analysis of 261,703 subjects.

BACKGROUND: Several genome-wide association studies already explored the associations between 6q25.1 rs2046210 polymorphism and breast cancer (BC), but the results of these studies were not consistent. Thus, we conducted a meta-analysis of relevant studies to better analyze the effects of rs2046210 polymorphism on individual susceptibility to BC. METHODS: PubMed, Web of Science, and Embase were searched for eligible studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Totally 21 studies with 261,703 subjects were analyzed. A significant association with BC was observed for the rs2046210 polymorphism in GG versus GA +AA (dominant comparison, p < 0.0001, OR = 0.78, 95% CI 0.73-0.83), AA versus GG + GA (recessive comparison, p < 0.0001, OR = 1.21, 95% CI 1.18-1.24), GA versus GG + AA (overdominant comparison, p < 0.0001, OR = 1.12, 95% CI 1.08-1.16), and G versus A (allele comparison, p < 0.0001, OR = 0.86, 95% CI 0.82-0.89). Further subgroup analyses yielded similar positive results in both Asians and Caucasians. CONCLUSION: In summary, our findings suggested that the rs2046210 polymorphism may serve as a potential genetic biomarker of BC in both Asians and Caucasians.

Cytotoxic anthraquinone dimers from Melandrium firmum.

Two new anthraquinone dimers, melrubiellin A (1) and melrubiellin B (2), were isolated from the aerial part of Melandrium firmum Rohrbach, along with seven known compounds (3-9). The structures of these compounds were elucidated by spectral analyses, including 1D and 2D NMR (COSY, HMQC, HMBC and NOESY) experiments. Compound 1 and 2 exhibited significant cytotoxicity towards HeLa, NCI-H460, Hep G2, Hep 3B and MKN-28 cell lines with IC50 values ranging from 5.26 to 81.16 µM.

Expression of Akt kinase-interacting protein 1, a scaffold protein of the PI3K/PDK1/Akt pathway, in pancreatic cancer.

OBJECTIVES: Akt kinase-interacting protein 1 (Aki1) has been reported to be a scaffold protein of the PI3K (phosphoinositide 3-kinase)/PDK1 (3-phosphoinositide-dependent protein kinase)/Akt pathway and to interact with epidermal growth factor receptor signaling. Although Aki1 has been reported to be expressed in lung cancer, the significance of its expression in pancreatic cancer has not been clarified. METHODS: The expression of Aki1 and its associated proteins was assayed in pancreatic cancer cell lines, and its involvement in cell viability was examined by treatment with Aki1 small interfering RNA. We also assessed the immunohistochemical expression of Aki1 in tissue samples from 60 patients with pancreatic cancer. RESULTS: All of the pancreatic cancer cell lines expressed Aki1 and its associated proteins at various levels. Treatment with Aki1 small interfering RNA or PI3K inhibitor inhibited the viability of Panc1 cells. Silencing of Aki1 in Panc1 cells reduced the phosphorylation of Akt and increased the phosphorylation of cleaved PARP. The Aki1 was expressed in 25 (42%) of the 60 pancreatic cancers, but there was no correlation between Aki1 expression and clinicopathologic parameters. We observed a statistically significant correlation between Aki1 and p-Akt expression (P = 0.016). CONCLUSIONS: Inhibition of the Aki1-Akt axis may be a therapeutic target in some patients with pancreatic cancer.

[The cytotoxicity and mechanism of CIK cells to breast cancer cells ZK-75-1].

AIM: To study the cytotoxicity and mechanism of cytokine-induced killer (CIK) cells to breast cancer cell line ZK-75-1. METHODS: The morphological changes of ZK-75-1 cells were observed by HE staining. The apoptosis of ZK-75-1 cell line was examined by TUNEL staining. The expression of P53, P16, C-myc, Bcl-2 and Bax was determined by immunocytochemical staining. RESULTS: The result of HE staining revealed that CIK cells moved toward the target cells, forming typical rosette cells. Granule-like substances appeared in cytoplasm of tumor cells, but only granule-shape patch was found in some tumor cells while breast cancer cells as control grew well. TUNEL staining indicated that the cells in control group were not stained or dyed well-distributed light blue. As the cells in experiment group became smaller, mucleoluser or perinuclear was dyed deep blue. The apoptotic rate of ZK-75-1 cells cocultured with CIK cells was increased after 4-12 hours and was decreased after 12-24 hours, with a significant difference compared with control group (P<0.01). Immunocytochemical staining showed that the expression of p53, p16, C-myc and Bcl-2 proteins in CIK group declined but the expression of Bax protein increased with the passage of time, which was significantly different compared with control (P<0.01). CONCLUSION: The mechanism of killing ZK-75-1 cells by CIK cells is closely related to the downregulation of the expression of P53, P16, c-myc and Bcl-2 proteins and to the upregulation of the expression of Bax protein. It also has close relation with the time of exposure to CIK cells.