Bioactive Peptides Sensitize Cells to Anticancer Effects of Oxaliplatin in Human Colorectal Cancer Xenografts in Nude Mice.

BACKGROUND: Despite new agent development and short-term benefits in patients with Colorectal Cancer (CRC), metastatic CRC cure rates have not improved due to high rates of oxaliplatin resistance and toxicity. There is an urgent need for effective tools to prevent and treat CRC and reduce morbidity and mortality of CRC patients. Exploring the effects of bioactive peptides on the antitumor to CRC was of vital importance to the clinical application. OBJECTIVE: This study aimed to investigate the therapeutic impact of Anticancer Bioactive Peptides (ACBP) on anticancer effect of oxaliplatin (LOHP) in human colorectal cancer xenografts models in nude mice. METHODS: HCT-116 cells were cultured in vitro via CCK-8 assays and the absorbance was measured at 450 nm. Apoptosis and cell cycle were assessed by Flow Cytometry (FCM) in vitro. HCT-116 human colorectal cancer cells inoculated subcutaneously in nude mice of treatment with PBS (GG), ACBP, LOHP, ACBP+LOHP (A+L) in vivo. The quality of life was assessed by dietary amount of nude mice, the weight of nude mice, inhibition rates, tumor weight and tumor volume. Immunohistochemistry and RT-qPCR method was conducted to determine the levels of apoptosisregulating proteins/genes in transplanted tumors. RESULTS: ACBP induced substantial reductions in viable cell numbers and apoptosis of HCT116 cells in combined with LOHP in vitro. Compared with the control GG group, ACBP combined low dose oxaliplatin (U) group demonstrated significantly different tumor volume, the rate of apoptosis, the expression levels of Cyt-C, caspase-3,8,9 proteins and corresponding RNAs (P<0.05). The expression of pro-apoptotic proteins in the cytoplasm around the nucleus was significantly enhanced by ACBP. Short term intermittent use of ACBP alone indicted a certain inhibitory effect on tumor growth, and improve the quality of life of tumor bearing nude mice. CONCLUSION: ACBP significantly increased the anti-cancer responses of low dose oxaliplatin (L-LOHP), thus, significantly improving the quality of life of tumor-bearing nude mice.

Selecting lncRNAs in gastric cancer cells for directed therapy with bioactive peptides and chemotherapy drugs.

Selecting lncRNAs for directed therapy with bioactive peptides and chemotherapy drugs may be an effective approach to treating gastric cancer (GC). We show genome-scale identification and characterization of differentially expressed lncRNAs in GC cells treated with a novel anti-cancer bioactive peptide (ACBP) and the chemotherapy drug oxaliplatin (ASLB). A total of 17,897 lncRNAs were identified through pairwise comparison, including 2,074 novel lncRNAs. Of those, 1,386 lncRNAs were differentially expressed (over 1.5-fold change vs. control, q-value < 0.05) in response to ACBP and ASLB treatment. These included 914 upregulated and 472 downregulated lincRNAs. Functional annotation of these lncRNAs through Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis revealed they activate metabolic pathways and protein-binding processes. Moreover, suppression of the DNA replication process and upregulation of AMP-activated protein kinase (AMPK) signaling in MKN45 cells exposed to ACBP alone or in combination with ASLB was predicted by hierarchical clustering analysis. By providing new insight into the transcriptomic effects of ACBP and ASLB in GC cells, these results provide the first evidence of ACBP inhibition of lincRNAs and may provide new mechanisms of action for ACBP and ASLB.

Bax is involved in the anticancer activity of Velcade in colorectal cancer.

Numerous chemotherapeutic agents promote tumor cell death by activating the intrinsic apoptosis signaling pathway. This pathway is regulated by mitochondrial dysfunction, which occurs through an intricate process controlled by complex interactions between B-cell lymphoma 2 (Bcl-2) family members and other cellular proteins. Bcl-2-associated X protein (Bax) is a proapoptotic protein that is an essential component of the intrinsic apoptosis signaling pathway. Patients lacking Bax may be less sensitive to chemotherapy due to an impaired intrinsic apoptosis signaling pathway. The present study demonstrated that Bax expression in colorectal cancer (CRC) tissues was typically increased compared with that in adjacent normal tissues. Furthermore, Bax-/- HCT-116 cells exhibited reduced proliferation and colony formation ability compared with Bax+/+ HCT116 cells, although the rate of apoptosis of these cells remained unchanged. However, Bax-/- HCT116 cells became more resistant to apoptosis when treated with Velcade. The results of the present study provide novel insights into the relevance of Bax expression to the prognosis of CRC.

Hepatoprotective Mongolian prescription II enhances the antitumor effects of chemotherapeutics in hepatocellular carcinoma xenografts.

Hepatoprotective Mongolian prescription II (MPII), a mixture of 18 different medicinal herbs, significantly inhibited the growth of human liver cancer cell lines Huh-7 and HepG2 in vitro with different concentrations; MPII (6mg/mL) inhibited cell proliferation by 80.48%. MPII induced apoptosis in both cell lines, which was observed by light microscopy and flow cytometry. MPII-induced apoptosis and G0/G1 cell cycle arrest were quantified by Annexin V-FITC/PI staining and flow cytometry. At the molecular level, MPII induced caspase-3, caspase-8, caspase-9, and cytochrome c gene expression. In vivo, MPII dramatically inhibited human liver tumor growth in a xenograft model in Kunming mice with no apparent cytotoxicity to the hosts. Apoptotic genes (Bcl-2 and Bax) are up-regulated, suggesting that the ratio of Bcl-2/Bax was statistically significant, indicating that the drugs had affected the expression of apoptosis genes, especially on induce apoptosis gene Bax. We also observed an attenuated effect when MPII was used in combination with chemotherapy drug 5-fluorouracil (5-FU). The mice treated with 5-FU alone did not show a concentration-dependent effect, but 5-FU in combination with MPII displayed concentration-dependent effects on liver cancer cells. Our study suggests that MPII works by inducing apoptosis and cell cycle arrest, and has the potential to be a powerful anticancer agent.

Expression and clinical implications of P53, P63, and P73 protein in malignant tumor of the parotid gland.

BACKGROUND/AIM: To investigate the expression of P53, P63, and P73 proteins in malignant parotid gland tumors and adjacent nonneoplastic tissues and the association between the 3 proteins and their clinical characteristics. MATERIALS AND METHODS: A total of 40 pairs of paraffin-embedded malignant parotid gland tumors and adjacent nonneoplastic tissues were collected. We detected P53, P63, and P73 protein expression by immunohistochemistry. Statistical analysis was performed by using the chi-square test. RESULTS: P53, P63, and P73 protein expression in malignant parotid gland tumors was higher than their expression in adjacent nonneoplastic tissue (P = 0.030, 0.001, and 0.001, respectively). Expression of P53, P63, and P73 proteins was not associated with age, sex, or lymph node metastasis (P > 0.05). Expression of P53 and P73 proteins, instead of the P63 protein, was correlated to the degree of malignancy (P = 0.026 and 0.018, respectively). There was no significant difference among the P53, P73, and P63 proteins in malignant parotid gland tumors (P > 0.05). In the follow-up, only one patient died of colon cancer. CONCLUSION: Our results suggest that the P53, P63, and P73 proteins may play a role in the development of malignant parotid gland tumors and provide data for their diagnosis.

Serum leptin concentrations in Mongolian women.

OBJECTIVE: The aim of our study is to elucidate the association between leptin and obesity in Mongolian women. METHOD: Total 181 women participated in the study including 118 Mongolians and 63 Han. Body mass index (BMI) was calculated by weight (kg) divided by square height (m²). Percent body fat (%fat) was detected by bioelectrical impedance analysis (BIA). Fasting serum leptin was determined by ELISA. RESULT: The average BMI and %fat of Mongolian and Han women was 25.14 ± 4.48 kg/m², 24.30 ± 3.62 kg/m² and 36.10 ± 6.23%, 33.84 ± 5.98%, respectively. Fasting serum leptin level in obese women (BMI ≥ 25) was remarkably higher than in normal weight women (18.5 < BMI < 25) in Mongolian and Han ethnic groups (all P < 0.001). Fasting serum leptin level in Mongolian women had borderline significance compared with it in Han women (P = 0.049). Multiple linear regression models revealed that ethnicity, %fat and BMI were associated with serum leptin concentrations independent of age. CONCLUSION: In Mongolian and Han women, fasting serum leptin level was positively associated with BMI and %fat (all P < 0.001).