Mechanism of polypeptide extract from scorpion venom inhibiting Hedgehog signaling transduction in K562/BALB/c-nu leukemia mice / 中草药

ABSTRACT

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.