Curcumin inhibited the growth and invasion of human monocytic leukaemia SHI-1 cells in?vivo by altering MAPK and MMP signalling

摘要

Context: Curcumin, a polyphenolic compound extracted from the rhizome of the tropical plant Curcuma longa L. (Zingiberaceae), has been considered as a cancer chemopreventive drug by American National Cancer Institute.Objective: To examine the effect of curcumin on acute monocytic leukaemia SHI-1 cells in?vivo.Materials and methods: The SHI-1 cells (1?×?10sup6/sup cells in 0.1?mL PBS) were injected subcutaneously into the right flanks of the female SCID mice. Curcumin dissolved in olive oil (15 and 30?mg/kg) was administered (i.p.) to mice once a day for 15?days while the control group received olive oil injection. Tumour proliferation and apoptosis were examined by PCNA, TUNEL and cleaved caspase-3 staining. The expression of MAPK, NF-κB, MMP9, MMP2 and vimentin were confirmed by RT-PCR, immunohistochemistry or western blotting.Results: Administration of curcumin significantly inhibited tumour growth, as the tumour weight decreased from 0.67?g (control) to 0.47?g (15?mg/kg) and 0.35?g (30?mg/kg). Curcumin inhibited the expression of PCNA and increased the degree of TUNEL and cleaved caspase-3 staining in tumour tissue. The results of western blotting showed that curcumin treatment inhibited NF-κB and ERK signalling while activating p38 and JNK. Moreover, curcumin attenuated the mRNA transcription and protein expression of MMP2 and MMP9. Curcumin also suppressed the level of vimentin.Discussion and conclusions: Our study demonstrates that curcumin can inhibit the growth and invasion of human monocytic leukaemia in?vivo, suggesting the possible use of curcumin for anti-metastasis in leukaemia and the value of determining its unique target.