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Inhibitory effect of EGFR antisense oligodeoxynucleotide on human hepatoma cell line
Zhi-Bing Gong1, Jing-Mei Liu, You-Ming Li
1Department of Gastroenterology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Background:
Hepatocellular carcinoma (HCC) is one of the most common cancer-related causes of death worldwide. The epidermal growth factor receptor (EGFR) is highly expressed in many human tumors and provides a new target for anticancer drug development. The aim of the present study was to explore the effect of EGFR antisense oligodeoxynucleotide on human HCC.
Methods:
SMMC-7721 cells in culture were treated with 10 mumol/L antisense-odn for 24, 48, 72 hours respectively and MTT assay was adopted to determine the proliferation of tumor cells in vitro. About 2 x 10(6) SMMC-7721 cells with or without pretreatment(30 micromol/L oligodeoxynucleotide) were inoculated into subcutaneous flap of 21 nude mice, of which 7 were treated with EGFR antisense-odn, 7 with scrambled oligodeoxynucleotide (scrambled-odn), and 7 not treated in vivo.
Results:
In vitro, after 24, 48, 72 hours the inhibitory rate of proliferation of SMMC-7721 cells treated with EGFR antisense-odn was 8%, 32%, and 34% respectively. In vivo after 8 weeks, no palpable tumor was found in 1/7 mice receiving cells pretreated with antisense-odn, whereas 7/7 untreated mice and 6/7 mice treated with scrambled-odn developed palpable tumors. Tumor growth in antisense-odn treated mice was significantly inhibited in comparison with that of those untreated (P < 0.01) or treated with scrambled-odn (P < 0.05).
Conclusions:
Antisense oligodeoxynucleotide acts as a specific growth inhibitor on SMMC-7721 in a sequence specific and time-dependent manner. EGFR antisense-odn can significantly inhibit the proliferation of human hepatoma cell in vitro as well as in vivo, indicating that EGFR may play an important role in the development of hepatoma and will be a new target for its treatment.
Insights
EGFR antisense oligodeoxynucleotide effectively inhibits human hepatocellular carcinoma (HCC) cell growth. This targeted therapy shows significant promise for treating HCC by blocking epidermal growth factor receptor (EGFR) proliferation in vitro and in vivo.
Area of Science:
- Oncology
- Molecular Biology
- Anticancer Drug Development
Background:
- Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally.
- Epidermal growth factor receptor (EGFR) is overexpressed in many tumors, presenting a therapeutic target.
- EGFR antisense oligodeoxynucleotide offers a potential strategy for HCC treatment.
Purpose of the Study:
- To investigate the efficacy of EGFR antisense oligodeoxynucleotide in inhibiting human HCC.
- To evaluate the impact of EGFR inhibition on HCC cell proliferation both in vitro and in vivo.
Main Methods:
- SMMC-7721 HCC cells were treated with EGFR antisense oligodeoxynucleotide in vitro.
- MTT assay was used to assess tumor cell proliferation.
- In vivo studies involved inoculating SMMC-7721 cells into nude mice, followed by treatment with EGFR antisense oligodeoxynucleotide, scrambled oligodeoxynucleotide, or no treatment.
Main Results:
- In vitro, EGFR antisense oligodeoxynucleotide demonstrated dose- and time-dependent inhibition of SMMC-7721 cell proliferation.
- In vivo, treatment with EGFR antisense oligodeoxynucleotide significantly suppressed tumor growth in nude mice compared to controls.
- No palpable tumors were observed in a portion of mice treated with EGFR antisense oligodeoxynucleotide.
Conclusions:
- EGFR antisense oligodeoxynucleotide acts as a sequence-specific and time-dependent inhibitor of HCC cell growth.
- EGFR plays a crucial role in hepatoma development, making it a viable therapeutic target.
- EGFR antisense oligodeoxynucleotide shows significant potential for the treatment of human HCC.
