Multidrug resistance reversal in human gastric carcinoma cells by neferine.
OBJECTIVE
To investigate the reversal effect of neferine on multidrug resistance in human gastric carcinoma cell line.


METHODS
Cells of a human gastric cancer cells line, SGC7901, and its vincristine (VCR) -resistant variant, SGC7901/VCR, were cultivated with or without neferine and/or VCR. The cytotoxic effect of VCR was evaluated by the MTT assay. Cell apoptosis induced by VCR was determined by flow cytometry (FCM). The expression of P-glycoprotein (P-gp) and a multidrug-resistance-associated protein (MRP) in cells was examined by immunofluorescence and FCM.


RESULTS
Neferine at the concentration from 2.5 micromol/L to 10 micromol/L had no cytotoxicity to SGC7901 cells, and its variant SGC7901/VCR cells. The IC50 of VCR against SGC7901 and SGC7901/VCR cells was 0.059 microg/mL and 2.32 microg/mL, respectively, indicating that SGC7901/VCR cells were 39 times more resistant to VCR than its parent SGC7901 cells. After treatment with neferine at concentrations of 2.5, 5 and 10 micromol/L, the IC(50) of VCR to SGC7901/VCR cell line decreased to 0.340, 0.128 and 0.053 microg/mL, respectively, thus, increased the chemosensitivity by 6.8-, 18.1- and 43.8-fold, respectively. SGC7901/VCR cells were apoptosis resistant to VCR. Neferine (2.5, 5 and 10 micromol/L) promoted the VCR-induced apoptosis of SGC7901/VCR cells in a dose-dependent manner. The expressions of P-gp and MRP were strongly positive in SGC7901/VCR cells, which were significantly down-regulated after treatment with neferine (10 micromol/L) for 24 h.


CONCLUSIONS
Neferine reverses multidrug resistance of human gastric carcinoma SGC7901/VCR cells, which may be associated with the down-regulations of P-gp and MRP expression in SGC701/VCR cells.
Cao
Jian-Guo
JG
Institute of Oncology, Nanhua University, Hengyang 421001, Hunan Province, China. caojianguocaojianguo48@hotmail.com
Tang
Xiao-Qing
XQ
Shi
Shu-Hong
SH
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D044182:Benzylisoquinolines / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D015536:Down-Regulation; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D014750:Vincristine / Q000494:pharmacology* / Q000627:therapeutic use
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014750:Vincristine; C057222:neferine