GSE193751
The combination of SLC7A11 inhibitor and oridonin synergistically inhibits cervical cancer cell growth by decreasing the NADPH/NADP+ ratio
Oridonin, as a natural terpenoids isolated from traditional Chinese medicinal herb Rabdosia rubescens, exhibits anticancer activity against multiple cancers with the IC50 ranging from 10 ¦ÌM to 100 ¦ÌM. We observed that SLC7A11 inhibitor Imidazole ketone erastin (1 ¦ÌM) potently increase the anti-proliferative activity of oridonin at low concentrations. Preliminary investigation demonstrated that combination of Imidazole ketone erastin (1 ¦ÌM) and oridonin induced apoptosis and ferroptosis only in a fraction of cells. To explore the synergistic anti-tumor mechanism of combination of oridonin and Imidazole ketone erastin, second-generation transcriptome sequencing(RNA-seq) was utilized to determine the transcriptome change in Hela cells affected by oridonin and Imidazole ketone erastin. PCA analysis showed that the group of oridonin or Imidazole ketone erastin alone located near the control group, while the group of combination gathered far away from the control group, indirectly indicating that combination of oridonin and Imidazole ketone erastin had synergistic biology function. Overall design: Hela cells were seeded in 6 well paltes, and treated with either 1) DMSO, 2) oridonin, 3) Imidazole ketone erastin, or 4) combination of  oridonin and Imidazole ketone erastin for 24 h. Total mRNAs of treated Hela cells were collected and sequenced on Illumina Novaseq 6000 and 150 bp paired-end reads were generated.