Related Experiment Video
Updated: Jun 22, 2025
Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery
Published on: April 26, 2024
Antitumor activity and transcriptome sequencing (RNA-seq) analyses of hepatocellular carcinoma cells in response to
Qiang Wang1, Fangchao Ma2, Jingchen Wang2
1Henan Biotechnology Development Center, BGI College & Henan Institute of Medical and Pharmaceutical Science, Zhengzhou University, Zhengzhou, 450052, China; High & New Technology Research Center, Henan Academy of Sciences, Zhengzhou, 450002, China; College of Pharmacy, Seoul National University, Seoul, 08820, South Korea.
Abstract:
Fifteen betulonic/betulinic acid conjugated with nucleoside derivatives were synthesized to enhance antitumor potency and water solubility. Among these, the methylated betulonic acid-azidothymidine compound (8c) exhibited a broad-spectrum of antitumor activity against three tested tumor cell lines, including SMMC-7721 (IC50 = 5.02 μM), KYSE-150 (IC50 = 5.68 μM), and SW620 (IC50 = 4.61 μM) and along with lower toxicity (TC50 > 100 μM) estimated by zebrafish embryos assay. Compared to betulinic acid (<0.05 μg/mL), compound 8c showed approximately 40-fold higher water solubility (1.98 μg/mL). In SMMC-7721 cells, compound 8c induced autophagy and apoptosis as its concentration increased. Transcriptomic sequencing analysis was used to understand the potential impacts of the underlying mechanism of 8c on SMMC-7721 cells. Transcriptomic studies indicated that compound 8c could activate autophagy by inhibiting the PI3K/AKT pathway in SMMC-7721 cells. Furthermore, in the xenograft mice study, compound 8c significantly slowed down the tumor growth, as potent as paclitaxel treated group. In conclusion, methylated betulonic acid-azidothymidine compound (8c) not only increases water solubility, but also enhances the potency against hepatocellular carcinoma cells by inducing autophagy and apoptosis, and suppressing the PI3K/Akt/mTOR signaling pathway.
