Fig. 6.

Synthetic lethality and regulation of xCT stability of H₂S mediated persulfidation of OTUB1 in vivo. (A) Combined treatment with AOAA and Erastin resulted in further decreased tumor volume compared with either alone. (**P < 0.01) (B) Combination of AOAA and Erastin induced further decreased H₂S levels in tumors. (*P < 0.05 vs Control, #P < 0.05 vs either Erastin or AOAA alone). (C) Combination induced further decreased persulfidation of OTUB1 in tumor cells. (D) Combination induced further decreased xCT levels and conjunction between OTUB1 and xCT. (E) and (F) Combination of AOAA induced further increased PTGS2 mRNA and MDA levels in tumors. (*P < 0.05 vs Control, #P < 0.05 vs either Erastin or AOAA alone). (G) Schematic diagram showing reciprocal regulation between xCT stability and the transsulfuration pathway before and after combined blocking with AOAA and Erastin.