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Objective To study the mechanism of the Hedgehog signaling transduction intervened by polypeptide extract from scorpion venom (PESV) on K562/BALB/c-nu leukemia mice. Trying to analyze the molecular mechanisms and targets of the inhibited effect of PESV on chronic myeloid leukemia (CML) in vivo. Methods After establishing the K562/BALB/c-nu leukemia mice successfully, the model mice were divided into six groups which were the blank group, the PESV high, medium, and low doses (0.3, 0.6, 1.2 mg/kg) group, the Imatinib (50 mg/kg) group, and the model group. After 14 d drug intervention, the levels of gene and protein expression of Hedgehog signaling pathway upstream factors Shh, Ptch, and Smo were detected by qRT-PCR and Western blotting, and the protein expression of downstream factor Gli1 was determined by ELISA test. Results Compared to the model group, the genetic and protein expression of Shh which was an upstream factor were increased in the PESV groups. The mRNA and protein expression of Ptch and Smo in PESV low-dose and medium-dose groups were decreased. There were no significant differences of upstream factors between Imatinib group and model group. The concentration of downstream Gli1 protein significantly decreased within low-dose and medium-dose PESV groups, while there was no significant difference between high-dose PESV group and Imatinib group. Conclusion PESV can inhibit the expression of Hedgehog signaling pathway upstream factor Ptch, Smo and downstream factor Gli1 on the mRNA and protein level, while Imatinib has no obvious inhibitory effect on the Hedgehog signaling pathway.
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Objective: To explore the inhibitory mechanism of polypeptide extract from scorpion venom (PESV) on sarcoma S180. Methods: Thirty mice were implanted with S180 cells and randomly divided into three groups: control group, PESV group, and rapamycin (RAPA) group with 10 mice in each group. Then the tumor volume growth curve was drawn and the tumor inhibitory rate (IR) was calculated. The morphological changes of the tumor tissue were observed by HE staining. The protein expression levels of Beclin1, MAP1LC3A, and CD133 were detected using immunohistochemical assay. Western blotting was applied to detecting the expression of Beclin1, MAP1LC3A, and CD133 in tumor tissue of mice in each group. Results: The growth of sarcoma S180 transplanted tumor was inhibited more obviously in the PESV group and RAPA group than that in the control group. The IR in the PESV and RAPA groups were 17.9% and 25.0%, respectively (P 180, the mechanisms might be associated with promoting the expression of autophagic relative factors, Beclin1 and MAP1LC3A as well as inhibiting the expression of CD133.
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Objective: To research the inhibitory mechanism of the polypeptide extract from scorpion venom (polypeptide extract from scorpion venom, PESV) on tumor growth, which would provides the theory basis for clinic treatment of malignant tumor. Methods: SKOV3 xenograft models were established, and tumors were excised after administration to observe the inhibitory effect of PESV. The effect of PESV on the tumor growth was observed by recording tumor growth curve and calculating the inhibitory rate; Immunohistochemistry and ELISA were applied to detect the levels of PTEN, PI3K, and P-Akt. Results: The inhibitory rates of the high-dose (20 mg/kg) and low-dose (10 mg/kg) PESV groups were 50.8% and 31.5%. Compared with the control group, the protein expressions of PI3K and P-Akt significantly decreased (P < 0.05 or 0.01) and the protein expressions of PTEN significantly increased (P < 0.05 or 0.01) in the high-and low-dose PESV groups. Conclusion: PESV could inhibit the growth of ovarian cancer. Its mechanisms might be associated with inhibiting the expressions of PI3K and P-Akt and increasing PTEN in the microenvironment of tumors.
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Objective: To identify the repopulation in metastatic Lewis lung adenocarcinoma during 5-Fu chemotherapy and observe the inhibition of polypeptide extract from scorpion venom (PESV) on the repopulation. Methods: To make repopulation model, Lewis cells were iv injected into caudal vein of C57BL/6 mice, the mice were ip injected by 5-Fu once every 7 d since day 7 and intervened by ig administration of PESV. Groups were treated differently. Six mice were sacrificed every 7 d, with counting metastatic foci in lung and detecting the level of proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), and microvessel dentity (MVD) expression in Lewis lung metastatic loci by using immunohistochemistry. Results: In model groups, from day 21 to day 28 the numbers of metastatic big loci increased 2.5 averagely, while from day 14 to day 21 increased 0.8 only; The weight of lung from day 21 to day 28 increased more than that from day 14 to day 21; The expression of PCNA was the lowest in day 21, the highest in day 28, and there was no significant difference between day 28 and day 14; The expression in both high- and low-dose PESV groups in day 28 was lower than that in model group. There was a significant effect in high-dose PESV group. In model group the expression of VEGF in day 28 was upregulated significantly (P<0.01 vs that in model group in day 21). Compared with model group, VEGF expression in high-dose PESV group in day 21 and day 28 was downregulated, especially in day 28 (P<0.01). In low-dose PESV group only in day 28 the difference was found (P<0.05 vs that in model group); The change of MVD was the same as PCNA. The expression was the lowest in day 21, the highest in day 28, and there was no significant difference between day 28 and day 14. While in high-dose PESV group, the number of MVD in day 14 was more than that in day 21, and in day 21 more than in day 28, there were significant differences. In low-dose PESV group, in day 14 more than in day 21, but no significant difference was found between day 21 and day 28. Conclusion: The phenomenon of repopulation acceleration is found in Lewis lung adenocarcinoma during 5-Fu treatment and PESV could inhibit the repopulation through anti-angiogenesis which may be one of the mechanisms of inhibiting tumor cell repopulation.