FIGURE 7.

Combination of siYTHDF2 and cisplatin enhanced the anti‐tumour effect of cisplatin in a chemoresistant PDX model of ICC. (A) The mRNA expression of YTHDF2 in HuCC‐T1 and HCCC‐9810 cells transfected with siControl or siYTHDF2 were measured by qRT‐PCR. (B) A graphic illustration of the construction of ICC PDX model. (C) Mice bearing passage 3 tumour of PDX0075 were randomly divided into four groups and treated with siControl (3nmol per mouse, twice a week), siYTHDF2 (3 nmol per mouse, twice a week), siControl plus cisplatin (siControl, 3 nmol per mouse, twice a week and cisplatin, 4 mg/kg, once a week) or siYTHDF2 plus cisplatin (siYTHDF2, 3 nmol per mouse, twice a week and cisplatin, 4 mg/kg, once a week) for 21 days, then were executed and photographed. (D) Tumour growth curves of each group were shown. Tumour volume was calculated twice a week. (E) Tumour weight of each group was measured. (F) Body weight of the mice was measured once a week. (G) Serum ALT of each group was measured. (H) Serum AST of each group was measured. (I) Serum CREA of each group was measured. (J) Serum BUN of each group was measured. (K) Representative IHC staining of CDKN1B and representative image of TUNEL in tumours with different treatments. (L) The graphical abstract illustrated that YTHDF2 recognised the m⁶A site on CDKN1B mRNA and accelerates its mRNA decay, which promotes tumourigenesis via accelerating cell cycle and desensitises ICC to cisplatin treatment via decreasing DNA damage, and then inhibiting apoptosis. The data are presented as mean ± SD and compared by t‐test. *p < .05; **p < .01; *** p < .001