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. 2022 Mar 10;30(7):2603–2617. doi: 10.1016/j.ymthe.2022.03.003

Figure 7.

Figure 7

Tadalafil produces a synergetic effect with DOX to impede breast cancer growth

(A) Xenograft mouse model of breast cancer treated with tadalafil and DOX. MDA-MB-231 cells were orthotopically implanted into the mammary fat pad (subcutaneously) of female athymic nude mice (n = 5–7/group). The mice were treated with tadalafil (2 mg/kg body weight) every day via gavage and DOX (2 mg/kg body weight) once a week via tail vein injection after the tumor volume had reached 100–150 mm3. Tumor volume was measured every 3 days, and the mice were euthanized 30 days after injection. ∗p < 0.05 and ∗∗p < 0.01. (B) Proliferation analysis of MDA-MB-231 cells with DOX resistance (MDA-MB-231-ADR) treated with 0.4 μg/mL DOX and 0, 25, 50, or 100 μM tadalafil for 24 h. (C) Tumor growth curves of MDA-MB-231-ADR cells orthotopically implanted into athymic nude mice that were treated with tadalafil and DOX as described in (A) (n = 5–7/group). (D) Two patient-derived xenograft (PDX) mouse models of breast cancer, UM1 and UM2. The models were treated with tadalafil and DOX as mentioned above (n = 5–7/group). Tumor volume was measured every 3 days, and the mice were euthanized 30 days after injection. (E) Dot-blot assay of RNA m6A methylation in breast cancer tumors harvested from PDX mouse models as indicated in (D) (n = 5–7/group). (F) RT-PCR analysis following m6A-IP of the BRCA1 mRNA 3′-UTR in MDA-MB-231 cells treated with 0.4 μg/mL DOX with or without 100 μM tadalafil for 24 h.