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. 2024 Aug 9;15(8):583. doi: 10.1038/s41419-024-06977-z

Fig. 6. Nanosac-encapsulated siRNA targeting NRF2 enhances antitumor efficacy of sorafenib.

Fig. 6

A Fluorescence microscopy of C11-BODIPY using Huh7 cells transfected with siDDX5 and incubated with Nanosac-encapsulated siCtrl or siNRF2 for 24 h, followed by addition of SOR (10 μM) for 24 h. Quantification by ImageJ software of the ratio of oxidized (510 nm)/non-oxidized (590 nm) C11-BODIPY. Data shown as mean ± SEM from 500 cells. *p < 0.05, **p < 0.01 by unpaired t-test. B Diagram illustrates treatment groups and timetable of intratumoral injection of Nanosac-encapsulated siRNAs. C Images of Huh7 xenograft tumors excised on day 19, following three intra-tumoral injections/week of indicated Nanosac-encapsulated siRNAs (3.0 µg siRNA/injection), and daily administration of SOR (80 mg/kg). Tumor weight of indicated treatment groups from eight tumors. *p < 0.05 by unpaired t-test. D RT-PCR quantification of NRF2 mRNA using total RNA isolated from Huh7 tumors treated with indicated Nanosac-encapsulated siRNAs ±SOR. Data expressed as mean ± SEM from eight tumors. *p < 0.05 by unpaired t-test. E Quantification of MDA and 4-HNE abundance using Huh7 xenograft tumors treated as indicated. Data expressed as mean ± SEM from eight tumors. **p < 0.01, ***p < 0.001 by unpaired t-test. F RT-PCR quantification of NRF2 mRNA using total RNA isolated from Dox-inducible Huh7-DDX5 tumors, -/+ Dox and SOR. Data expressed as mean ± SEM from indicated number of tumors in each group. *p < 0.05, **p < 0.01 by unpaired t-test. G Immunoblots of DDX5 and p62/SQSTM1 using lysates from Dox-inducible Huh7-DDX5 tumors, -/+ Dox and SOR administration (80 mg/kg, 5 days per week), as described in Li et al., [7]. Quantification by imageJ software of p62/SQSTM1. Data expressed as mean ± SEM from eight tumors. *p < 0.05 by unpaired t-test.