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COX-2/PTGS2-targeted herbal-derived oligonucleotide drug HQi-sRNA-2 was effective in spontaneous mouse lung cancer
Yexuan Lin1, Na Sun1, Dengyuan Liu1
1State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Abstract:
In 2020, the number of deaths caused by lung cancer worldwide reached 1,796,144, making it the leading cause of cancer-related deaths. Cyclooxygenase-2/prostaglandin endoperoxide synthase 2 (COX-2/PTGS2) is overexpressed in lung cancer, which promotes tumor proliferation, invasion, angiogenesis, and resistance to apoptosis. Here, we report that the oligonucleotide drug HQi-sRNA-2 from Traditional Chinese Medicine Huangqin targeting COX-2/PTGS2 significantly inhibited proliferation, migration, and invasion and induced apoptosis in the human lung cancer cell line NCI-H460. Oral delivery of HQi-sRNA-2 bencaosomes prolonged survival, reduced tumor burden, and maintained weight in a spontaneous mouse lung cancer model. Compared with paclitaxel, HQi-sRNA-2 may be less toxic and have approximately equal efficacy in reducing tumor burden. Our previous studies reported that herbal small RNAs (sRNAs) are functional medical components. Our data suggest that sphingosine (d18:1)-HQi-sRNA-2 bencaosomes, targeting COX-2/PTGS2 and downregulating the PI3K and AKT signaling pathways, may provide novel therapeutics for lung cancer.
Insights
An oligonucleotide drug derived from Traditional Chinese Medicine, targeting COX-2/PTGS2, shows promise in treating lung cancer by inhibiting tumor growth and inducing apoptosis. This novel therapy may offer a less toxic alternative to existing treatments.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Lung cancer is a leading cause of cancer death globally.
- Overexpression of Cyclooxygenase-2/prostaglandin endoperoxide synthase 2 (COX-2/PTGS2) is linked to lung cancer progression.
- Traditional Chinese Medicine components are being explored for novel cancer therapies.
Purpose of the Study:
- To investigate the anti-cancer effects of the oligonucleotide drug HQi-sRNA-2 targeting COX-2/PTGS2.
- To evaluate the efficacy and safety of HQi-sRNA-2 in preclinical lung cancer models.
- To explore the therapeutic potential of HQi-sRNA-2 in combination with sphingosine bencaosomes.
Main Methods:
- In vitro studies using the human lung cancer cell line NCI-H460.
- In vivo studies using a spontaneous mouse lung cancer model with oral administration of HQi-sRNA-2 bencaosomes.
- Comparison of HQi-sRNA-2 efficacy with paclitaxel.
- Analysis of PI3K and AKT signaling pathway modulation.
Main Results:
- HQi-sRNA-2 significantly inhibited proliferation, migration, and invasion while inducing apoptosis in NCI-H460 cells.
- Oral delivery of HQi-sRNA-2 bencaosomes prolonged survival, reduced tumor burden, and maintained weight in mice.
- HQi-sRNA-2 demonstrated comparable efficacy to paclitaxel in reducing tumor burden with potentially lower toxicity.
- The treatment downregulated the PI3K and AKT signaling pathways.
Conclusions:
- HQi-sRNA-2 is a potent inhibitor of lung cancer cell proliferation and invasion.
- Sphingosine-HQi-sRNA-2 bencaosomes represent a promising oral therapeutic strategy for lung cancer.
- This novel approach targeting COX-2/PTGS2 offers a potential new avenue for lung cancer treatment with improved safety profile.
