Interaction of Estradiol and Endoplasmic Reticulum Stress in the Development of Esophageal Carcinoma.

Gender differences in esophageal cancer patients indicate that estradiol may have antitumor effects on esophageal cancer. The initiation of endoplasmic reticulum stress (ERS) can induce apoptosis in esophageal cancer cells. However, it is still unknown whether estradiol inhibits the development of esophageal cancer by activating ERS pathway. In this study, the gender difference in the development of esophageal cancer was observed by analyzing clinical data and the experimental tumor xenografts in mice. Meanwhile, we investigated the mechanism of ERS in estradiol-mediated inhibition of esophageal cancer using esophageal squamous cell carcinoma cell line EC109. The proportion of male patients with esophageal cancer was significantly higher than female patients. Meanwhile, male patients were prone to have adventitial invasion. The weight of transplanted tumors in female mice was significantly smaller than that in male mice. In vitro experiments showed estradiol inhibits the viability and migration of EC109 cells by increasing the expression of ERS-related proteins, whereas ERS inhibitor 4-PBA abolished the effects of estradiol. In conclusion, our data demonstrate that sex difference exists in the occurrence of esophageal cancer. Estradiol can inhibit the viability and migration of esophageal cancer cells through the activation of ERS, providing a novel insight for esophageal cancer development, treatment, and prevention.

Expression and significance of TMSG-1 in esophageal squamous carcinoma and EC109 cells / 西安交通大学学报(医学版)

Objective To study the expression and significance of tumor metastasis suppressor gene-1(TMSG1) in esophageal squamous cell carcinoma (ESCC) and EC109 cells.Methods Immunohistochemistry S-P method was used to examine the expression of TMSG-1 protein in 136 cases of ESCC and 37 cases of normal esophageal mucosa.We analyzed the relationship between TMSG-1 and clinicopathological data of ESCC patients.EC109 cells were treated with 3 μg/mL of cisplatin (CDDP) in vitro for 24 h (the intervention group) and the control group was set up at the same time.The proliferation-inhibitory capability was analyzed with MTT assay.RT-PCR was used to examine the expression of TMSG-1 in the intervention group and the control group.Results The positive rate of TMSG-1 in ESCC and normal esophageal mucosa was 52.2％ (71/136) and 94.6％ (35/37),respectively.The expression of TMSG-1 in ESCC was significantly lower than that in normal esophageal mucosa (P＜0.05).The expression of TMSG-1 was related to TNM stage,differentiation degree and lymph node metastasis (P＜0.05).After EC 109 cells were treated with CDDP for 24 h,the proliferation inhibition rate was increased significantly compared with the control group (P＜0.01).RT-PCR results showed that the expression of TMSG-1 in the cells of the intervention group was significantly higher than that in the control group (P＜ 0.01).Conclusion The abnormal expression of TMSG-1 may play a role in the development and metastasis of ESCC.Examination of TMSG-1 may be useful for making diagnosis and guiding clinical therapy of ESCC.

Curcumin inhibits Ec109 cell growth via an AMPK-mediated metabolic switch.

AIMS: Glycolytic enzymes are always greatly increased in cancer cells. Whether metabolic reprogramming is involved in curcumin-mediated inhibition of cancer cell growth is unknown. MAIN METHODS: In this study, cell viability was assayed with MTS analysis; cell cycle was measured with flow cytometry analysis. RT-PCR and western blotting were used to analyse the mRNA and protein expression, respectively. KEY FINDINGS: Here we demonstrated that curcumin inhibited cancer cell growth, especially for Ec109 cells. Curcumin induced cell cycle arrest at G2/M phase. Curcumin caused a significant down-regulation of glycolytic enzymes expressions in a dose-dependent manner. Our results further indicated that the AMPK was required for curcumin-mediated down-regulation of glycolytic enzymes. AMPK-mediated down-regulation of glycolytic enzymes blocked Ec109 cell growth. SIGNIFICANCE: Taken together, our results revealed that the AMPK-mediated metabolic switch plays an important role in esophageal cancer cell growth.

Activated Notch1 signaling inhibits growth of EC109 cell line and its mechanism / 中国癌症杂志

Background and purpose: It has been reported that activation of Notch1 could strongly inhibit proliferation of HPV (human papilloma virus)-positive HeLa cells by down-regulation of the E6 and E7 genes. The aim of this paper was to investigate the role of the Notch signaling pathway in growth arrest of EC109 cells in vitro and the molecular mechanism. Methods: EC109 cell lines, a well differentiated human ESCC (esophageal squamous cell carcinoma) cell line with HPV18-positive, was used in the study. Exogenous intracellular domain of Notch1(ICN) was transfected into cultured EC109 cells by lipofectamine transfection, the proliferation of the transfected cells was measured by an MTT assay. Cell cycle distribution was analyzed by flow cytometry. Human papilloma virus type 18 (HPV18) E6/E7 mRNA expression was detected by RT-PCR, and p53 protein expression was detected by Western blot.Results: Activation of Notchl signaling resulted in inhibition of EC109 cell proliferation with the induction of G_2/ M arrest. There was a significant difference in terms of the percentage of G_2/M phase cells among the ICN-transfected group (42.57±1.57)% and the non-transfected group (1.88±0.66)% or the empty plasmid transfected group (1.99±1.02)% (P<0.01). Down modulation of HPV18 E6/E7 gene expression and upregulation of p53 expression was (2.15±0.23) in ICN-transfected group higher than non- transfected group (0.45±0.07) and empty plasmid transfected group (0.46±0.02) (P<0.01). Conclusion: Repression of HPV18 E6/E7 expression by Notch1 signaling results in growth suppression of HPV18-positive EC109 cells with concomitant activation of p53-mediated pathways.