[Study on the antisense inhibition effect of liposome-mediated radiolabled antisense oligonucleotides of c-myc mRNA]
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Published on: June 15, 2018
Jianguo Zheng1, Tianzhi Tan, Weimin Pan
1Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Objective:
To ascertain whether liposome-mediated antisense oligonucleotides could inhibit the cancer cells from growing and the oncogene from expressing.
Methods:
The antisense, sense and scrambled oligonucleotides for c-myc mRNA, each containing 15 bases, were synthesized elsewhere and were labeled with 99m-technetium (99mTc-DNA). Some of them were encapsulated with liposome. Then the 99mTc-DNA and the 99mTc-DNA entrapped with liposome were transfected into colon cancer cells, LS-174-T, with different radioactivity concentrations. At different time after transfection the uptake rate of cells was measured, and the reflow rate was detected at 18 h. Inhibition effect on cellular growth was tested by MTT colorimetric experiment and on the expression of c-myc by flow cytometry.
Results:
The cellular uptake rate increased gradually after transfection within 5 hours, and that of liposome-mediated 99mTc-DNA was significantly higher than that of 99mTc-DNA. The reflow rate and fluorescence intensity of oncoprotein were 39.51 percent and 2.9860 +/- 0.3733 for antisense oligonucleotides, 44.12 percent and 4.2600 +/- 0.2218 for sense oligonucleotides, and 63.92 percent and 5.2620 +/- 0.8562 for mismatched oligonucleotides. The reflow rate and fluorescence intensity of liposome-entrapped 99mTc-labeled antisense oligonucleotide were significantly lower than those of sense and scrambled oligonucleotides.
Conclusion:
The liposome-mediated 99mTc-labeled antisense oligonucleotides could prohibit the cancer cells from growing and the oncogene from expressing.
Insights
Liposome-mediated antisense oligonucleotides effectively inhibited colon cancer cell growth and oncogene expression. This novel delivery method enhances therapeutic potential for cancer treatment.
Area of Science:
- Molecular Biology
- Nanotechnology
- Oncology
Context:
- Antisense oligonucleotides offer targeted gene silencing for cancer therapy.
- Liposome encapsulation enhances oligonucleotide delivery and stability.
- The c-myc oncogene is a key target in colon cancer progression.
Purpose:
- To evaluate the efficacy of liposome-mediated antisense oligonucleotides in inhibiting colon cancer cell growth.
- To assess the impact of liposome delivery on antisense oligonucleotide uptake and oncogene expression inhibition.
Summary:
- Antisense, sense, and scrambled oligonucleotides targeting c-myc mRNA were synthesized and labeled with 99mTc.
- Liposome-encapsulated and non-encapsulated 99mTc-labeled oligonucleotides were transfected into LS-174-T colon cancer cells.
- Liposome-mediated delivery significantly increased cellular uptake and demonstrated superior inhibition of cell growth and c-myc expression compared to non-liposomal delivery.
Impact:
- Liposome-mediated delivery of antisense oligonucleotides represents a promising strategy for cancer therapy.
- This approach can effectively reduce cancer cell proliferation and oncogene expression.
- Further research may lead to improved targeted cancer treatments with reduced side effects.
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