[Study on synergistic anti-tumor effect of Shuangdan Capsules combined with 5-FU on hepatocellular carcinoma cells Huh-7 and xenograft mice].

This paper discussed the synergistic anti-tumor effect of Shuangdan Capsules combined with 5-fluorouracil(5-FU) on human liver cancer cell line Huh-7 and tumor bearing mice. The effects of Shuangdan Capsules combined with 5-FU on the activity and vascular endothelial growth factor(VEGF) receptor protein expression of Huh-7 cells were investigated, and the effects of drug combination on tube formation of HUVEC cell were also verified. In addition, the mice model of Huh-7 was established to observe the anti-tumor effect of drug combination and the distribution of tumor blood flow in tumor bearing mice by using molecular imaging. HPLC analysis showed that Shuangdan Capsules mainly consisted of danshensusodium, protocatechuic aldehyde, paeoniflorin, rosmarinic acid, alkannic acid, salvianolic acid B, and paeonol. In MTT experiment, the inhibition rate of Shuangdan Capsules(20 mg·L~(-1)) and 5-FU(1 µmol·L~(-1)) on Huh-7 cells was 60%, and the CI value was 0.59, suggesting that these two drugs had synergistic anti-hepatoma cells effect. The expression of VEGF receptor in Huh-7 cells was inhibited by the combination of these two drugs. In addition, the process of HUVEC was slow, and the number, length and area of the lumen branches decreased significantly. In vivo, Shuangdan Capsules combined with 5-FU inhibited the growth and prolongation of survival of Huh-7 cells in subcutaneous transplanted tumor nude mice; serum expression of CD31 and VEGF in nude mice were decreased, while caspase-3 was increased. Meanwhile, the drug combination significantly inhibited the expressions of MMP2 and VEGF in tumor tissues. Ultrasound showed that Shuangdan Capsules combined with 5-FU also inhibited tumor angiogenesis and reduced blood flow of tumor tissue. The results showed that Shuangdan Capsules combined with 5-FU may inhibit tumor angiogenesis by inhibiting VEGF and MMP2 expressions, thereby blocking tumor growth.

Overexpression of Lysine-Specific Demethylase 1 Is Associated With Tumor Progression and Unfavorable Prognosis in Chinese Patients With Endometrioid Endometrial Adenocarcinoma.

OBJECTIVE: Lysine-specific demethylase 1 (LSD1) is a kind of flavin adenine dinucleotide-dependent amine oxidase that regulates normal cellular differentiation, gene activation, tumorigenesis, and progression. This study aims to detect the expression level of LSD1 in endometrial cancer and to explore its role in the progression and prognosis of endometrioid endometrial adenocarcinoma (EEA). METHODS: Immunohistochemistry was used to examine the expression of LSD1 in 206 EEA specimens, 50 benign endometrial lesion specimens, and 45 normal endometrium specimens. χ Analysis, Kaplan-Meier method, and multivariate Cox proportional hazard analysis were applied for the statistical analysis. RESULTS: Compared with normal endometrium and benign endometrial lesion (both P < 0.001), LSD1 was overexpressed in EEA. LSD1 expression was correlated with histological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, vascular/lymphatic invasion, depth of myometrial invasion, and lymph node metastasis. Results of the Kaplan-Meier analysis indicated that LSD1 expression was associated with overall survival (OS) and disease-free survival (DFS) of EEA. The negative expression LSD1 group had longer OS and DFS than did the positive expression group. The difference was significant (both P < 0.001, log-rank test). Multivariate Cox regression analysis revealed that the LSD1 expression status was an independent prognostic factor for both OS (P = 0.027) and DFS (P = 0.016) of patients with EEA. CONCLUSIONS: Overexpression of LSD1 may contribute to the progression of EEA and may thus serve as a new biomarker to predict the prognosis of EEA.

Raloxifene suppress proliferation-promoting function of estrogen in CaSKi cervical cells.

Raloxifene has demonstrated anti-estrogen activity in reproductive organs and tissues, but there are very few related studies in cervical cells. The aims of this study is to explore the function of raloxifene in CaSKi cervical cells. We examined the effects of raloxifene on cervical cancer cells exposed to estrogen. The effect of Raloxifene on cell growth, apoptosis was detected. The human papillomavirus (HPV) 16 E6E7 transcription in cervical cell line CaSki cells exposed to 17-estradiol was also examined. Apoptosis was measured by endonucleolytic degradation of DNA. HPV 16 E6E7 was measured by northern analysis. The results indicated that raloxifine inhibits estrogenic promotion activity on growth of CaSki cells. Raloxifene suppresses the proliferation promotion activity of estradiol in CaSki cells. Raloxifene suppresses the stimulation effect of estradiol on HPV 16 E6E7 transcription in CaSki cells. In conclusion, raloxifene inhibit the CaSki cells proliferation induced by estradiol, which suggests that raloxifine also has anti-estrogen activity in cervical cells.

DNA methylation and carcinogenesis of PRDM5 in cervical cancer.

OBJECTIVE: PR (PRDI-BF1 and RIZ) domain proteins (PRDM) are a subfamily of the kruppel-like zinc finger gene products and play key roles during cell differentiation and malignant transformation. PRDM5 (PR domain containing 5 PFM2) is a new PR-domain-containing gene. The purpose of the present study was to examine the expression of PRDM5 and evaluate its carcinogenesis in cervical cancer. The relationship between DNA methylation and transcriptional silencing of PRDM5 was investigated in cervical cancer. METHODS: PRDM5 expression was examined in cervical cancer cell lines and cervical tissues (12 normal and 42 cancerous) by using RT polymerase chain reaction (PCR). Methylation status of the PRDM5 promoter was studied using methylation-specific PCR (MSP). RESULTS: PRDM5 expression is reduced or lost in cervical cancers, compared with normal cervical tissues (P < 0.05). The current study results also showed that loss of PRDM5 is mediated by aberrant cytosine methylation of the PRDM5 promoter. There were 40.5% of carcinomas methylated, while none of normal tissues were methylated. PRDM5 mRNA expression was significantly higher (P = 0.000) in unmethylated (0.2634 ± 0.0674, mean ± SD), compared with methylated tissues (0.1007 ± 0.0993, mean ± SD). Last, treatment with a DNA methyltransferase inhibitor led to reactivation of PRDM5 expression in cell lines that had negligible PRDM5 expression at baseline. CONCLUSIONS: Reduced expression of PRDM5 may play an important role in the pathogenesis and/or development of cervical cancer, and is considered to be caused in part by aberrant DNA methylation.