Abstract | BACKGROUND AND OBJECTIVE: METHODS: The effects of SAM on the proliferation of gastric cancer SGC-7901 and MKN-45 cells were determined by MTT assay. After SGC-7901 and MKN-45 cells were treated with 0, 2, and 4 mmol/L SAM for 72 h, the expression and methylation of c-myc and urokinase type plasminogen activator (uPA) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP). Tumor xenografts were established by injecting SGC-7901 cells subcutaneously in BALB/c nude mice. The mice were randomized into low concentration group [192 µmol/(kg · day)], high concentration group [768 µmol/(kg · day)], and control group [ normal saline (NS)], and received peritoneal injection of relative reagents for 15 days. The tumor size was measured, the protein and mRNA expression of c-myc and uPA were detected by immunohistochemistry and RT-PCR, and the methylation of c-myc and uPA genes was detected by MSP. RESULTS: SAM inhibited the growth of SGC-7901 and MKN-45 cells obviously and the effects were enhanced with the increase of SAM concentration and treatment time. The mRNA expression of c-myc and uPA in SGC-7901 cells and that of uPA in MKN-45 cells significantly decreased. The c-myc and uPA genes in SGC-7901 cells and uPA gene in MKN-45 cells were partly or completely methylated after SAM treatment. The tumor volume was significantly lower in low concentration group [(618.51 ± 149.27) mm³] and high concentration group [(444.32 ± 118.51) mm³] than in control group [(1018.22 ± 223.07) mm³] (both P < 0.01). The inhibitory rates of tumor growth were 39.26% in low concentration group and 56.36% in high concentration group. The protein and mRNA expressions of c-myc and uPA were remarkably reduced (all P < 0.01), and the hypomethylation of c-myc and uPA genes were reversed after SAM treatment. CONCLUSIONS: SAM can inhibit the growth of human gastric cancer cells both in vivo and in vitro. The mechanism may be that SAM can reverse the hypomethylation of c-myc and uPA genes, reduce their expression, and then inhibit tumor growth.
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Authors | Ye Zhao, Jian-Sheng Li, Ming-Zhou Guo, Bai-Sui Feng, Jin-Ping Zhang |
Journal | Chinese journal of cancer
(Chin J Cancer)
Vol. 29
Issue 8
Pg. 752-60
(Aug 2010)
ISSN: 1000-467X [Print] England |
PMID | 20663323
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- MYC protein, human
- Proto-Oncogene Proteins c-myc
- RNA, Messenger
- S-Adenosylmethionine
- Urokinase-Type Plasminogen Activator
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- DNA Methylation
- Dose-Response Relationship, Drug
- Female
- Humans
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Neoplasm Transplantation
- Proto-Oncogene Proteins c-myc
(genetics, metabolism)
- RNA, Messenger
(metabolism)
- S-Adenosylmethionine
(pharmacology)
- Stomach Neoplasms
(metabolism, pathology)
- Tumor Burden
(drug effects)
- Urokinase-Type Plasminogen Activator
(genetics, metabolism)
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