Matrine inhibits invasiveness and metastasis of human malignant melanoma cell line A375 in vitro.
BACKGROUND
Matrine is a traditional Chinese medicine with significant inhibitory activity against malignant tumors. Its effects on the invasiveness and metastasis of malignant tumors have rarely been reported.


OBJECTIVE
To investigate whether matrine can inhibit the metastasis-related activities of the human malignant melanoma cell line A375 in vitro.


METHODS
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and Annexin-V-fluorescein isothiocyanate/propidium iodide (Annexin-V-FITC/PI) affinity assay were used to examine the effects of matrine on the proliferation and apoptosis induction of A375 cells. The morphologic changes of A375 cells were observed by light and electron microscopy. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were performed to evaluate the expression of heparanase mRNA and protein. The effect of matrine on the adhesion ability and invasiveness of treated A375 cells was tested by cell-Matrigel adhesion assay and Matrigel invasion assay, respectively.


RESULTS
Matrine showed significant inhibition of the proliferation of A375 cells in a dose- and time-dependent manner. It also induced apoptosis in a dose-dependent manner. Compared with the control group, the levels of heparanase mRNA and protein expression of A375 cells treated with different concentrations of matrine were decreased significantly, as were their adhesion ability and invasiveness.


CONCLUSIONS
These findings indicate that matrine inhibits the invasiveness and metastasis of A375 cells in vitro. The mechanisms may be linked to the inhibition of cellular proliferation, induction of apoptosis, and downregulation of heparanase mRNA and protein expression.
Liu
Xiao-Yan
XY
Department of Dermatology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Fang
Hong
H
Yang
Zheng-Gang
ZG
Wang
Xiao-Yong
XY
Ruan
Li-Ming
LM
Fang
De-Ren
DR
Ding
Ying-Guo
YG
Wang
Yi-Na
YN
Zhang
Yu
Y
Jiang
Xiao-Ling
XL
Chen
Hong-Chao
HC
D000470:Alkaloids / Q000494:pharmacology*; D000704:Analysis of Variance; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008516:Medicine, Chinese Traditional; D008545:Melanoma / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009362:Neoplasm Metastasis / Q000517:prevention & control; D008517:Phytotherapy; D010946:Plants, Medicinal / Q000737:chemistry; D011807:Quinolizines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029909:Sophora / Q000737:chemistry; D000093842:Matrines; D000099175:Heparanase
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D005966:Glucuronidase; D011807:Quinolizines; D012333:RNA, Messenger; D000093842:Matrines; D000099175:Heparanase