Fig. 7: Targeting SPHK1 and S1PR3 with inhibitors suppress growth of TSC2-deficient cell xenograft tumors. | Cell Death & Disease

Fig. 7: Targeting SPHK1 and S1PR3 with inhibitors suppress growth of TSC2-deficient cell xenograft tumors.

From: Targeting SPHK1/S1PR3-regulated S-1-P metabolic disorder triggers autophagic cell death in pulmonary lymphangiomyomatosis (LAM)

Fig. 7

Female SCID mice were inoculated with ELT3-V3 cells (stably expressing luciferase tag) subcutaneously. Tumor-bearing mice were intraperitoneally administered vehicle control, PF543 (2 mg/kg, four times per week) or TY52156 (2 mg/kg, four times per week). A Animals were given D-luciferin (200 μL per 20 g body weight, i.p.) before bioluminescence imaging was performed at the indicated times. Luminescence color scale: 0 week-5 week (min = 1 × 107, max = 1 × 108). The statistical analysis in the right panel indicates the photon flux. Relative photon flux was measured using Perkin Elmer software. The results are representative of five mice per group. B The size of subcutaneous tumors was measured after 5 weeks of treatment (upper panel), and the tumor weights were quantified (lower panel). C, D Immunoblot analysis of SPHK1 or S1PR3, phosphor-62, LC3I/LC3II and phosphor-S6 (Ser235/236) in xenograft tumors treated with vehicle control, PF543 or TY52156 was performed. Three tumors were randomly selected in each group. E Gene expression of SQTSM1, ATG5 and ATG7 in the xenograft tumors was detected by RT-PCR. The results represent tumors from five mice per group. F Analysis of the apoptosis rate was performed using a TUNEL kit with xenograft tumors treated with vehicle control, PF543 or TY52156. G H&E and IHC staining of SPHK1, S1PR3, ASAH1, p62, cl-caspase 3, beclin-1, and Ki67 in xenograft tumors of ELT3-V3 cells treated with vehicle control, PF543, or TY52156. The results represent tumors from five mice in each group. Student’s t test, *P < 0.05 and **P < 0.01.

Back to article page