Journal: Drug Design, Development and Therapy

Article Title: Overexpression of PI3K p110α contributes to acquired resistance to MET inhibitor, in MET-amplified SNU-5 gastric xenografts

doi: 10.2147/dddt.s89410

Figure Lengend Snippet: Figure 1 Establishment of MET inhibitor-resistant human gastric cancer model in vivo. Notes: (A) Nude mice-bearing SNU-5 tumors were once-daily orally dosed with 10 mg/kg PHA665752 for up to 26 weeks. Tumor volume was monitored twice weekly. (B) Nude mice-bearing SNU-5 tumors after 26 weeks treatment. (C) Tumors were resected from nude mice. (D) The expression level of PI3K p110α, β, γ, p-MET, PTEN, and DNA-PK were analyzed by Western blotting in parental and PHA665752-resistant SNU-5 xenografts.

Article Snippet: reagents and antibodies A selective PI3K p110α inhibitor PI-103 and MET selective inhibitor PHA665752 were purchased from Selleck Chemicals (Houston, TX, USA).

Techniques: In Vivo, Expressing, Western Blot

Journal: Drug Design, Development and Therapy

Article Title: Overexpression of PI3K p110α contributes to acquired resistance to MET inhibitor, in MET-amplified SNU-5 gastric xenografts

doi: 10.2147/dddt.s89410

Figure Lengend Snippet: Figure 3 Antitumor effects of PHA665752 in combination with PI-103 in PHA665752-resistant SNU-5 xenografts. Notes: (A) Nude mice-bearing resistant SNU-5 tumors were orally dosed with 10 mg/kg PHA665752 once daily or/and 5 mg/kg PI-103 once daily by oral administration for 3 weeks, respectively. The tumor volumes were monitored twice weekly. (B) Mice were killed using CO2 on the last day of efficacy. (C) Tumor weight was measured on the last day of efficacy. (D) Body weights of mice were monitored in the indicated day during the efficacy study. (E) Effects of PHA665752 or/and PI-103 on signaling transduction pathways between parental and PHA665752-resistant SNU-5 xenografts model. The expression level of p-MET, p-AKT, p-ERK, p-S6, p110α, β, γ, DNA-PK, PTEN, and p53 were analyzed by Western blotting in parental and PHA665752-resistant SNU-5 xenografts after exposing to PHA665752 or/and PI-103. Mean ± SD, n=10. **P,0.01 vs vehicle group. Abbreviation: SD, standard deviation.

Article Snippet: reagents and antibodies A selective PI3K p110α inhibitor PI-103 and MET selective inhibitor PHA665752 were purchased from Selleck Chemicals (Houston, TX, USA).

Techniques: Transduction, Expressing, Western Blot, Standard Deviation

Journal: Drug Design, Development and Therapy

Article Title: Overexpression of PI3K p110α contributes to acquired resistance to MET inhibitor, in MET-amplified SNU-5 gastric xenografts

doi: 10.2147/DDDT.S89410

Figure Lengend Snippet: Establishment of MET inhibitor-resistant human gastric cancer model in vivo. Notes: ( A ) Nude mice-bearing SNU-5 tumors were once-daily orally dosed with 10 mg/kg PHA665752 for up to 26 weeks. Tumor volume was monitored twice weekly. ( B ) Nude mice-bearing SNU-5 tumors after 26 weeks treatment. ( C ) Tumors were resected from nude mice. ( D ) The expression level of PI3K p110α , β , γ , p-MET, PTEN, and DNA-PK were analyzed by Western blotting in parental and PHA665752-resistant SNU-5 xenografts.

Article Snippet: A selective PI3K p110 α inhibitor PI-103 and MET selective inhibitor PHA665752 were purchased from Selleck Chemicals (Houston, TX, USA).

Techniques: In Vivo, Expressing, Western Blot

Journal: Drug Design, Development and Therapy

Article Title: Overexpression of PI3K p110α contributes to acquired resistance to MET inhibitor, in MET-amplified SNU-5 gastric xenografts

doi: 10.2147/DDDT.S89410

Figure Lengend Snippet: Antitumor effects of PHA665752 in combination with PI-103 in PHA665752-resistant SNU-5 xenografts. Notes: ( A ) Nude mice-bearing resistant SNU-5 tumors were orally dosed with 10 mg/kg PHA665752 once daily or/and 5 mg/kg PI-103 once daily by oral administration for 3 weeks, respectively. The tumor volumes were monitored twice weekly. ( B ) Mice were killed using CO 2 on the last day of efficacy. ( C ) Tumor weight was measured on the last day of efficacy. ( D ) Body weights of mice were monitored in the indicated day during the efficacy study. ( E ) Effects of PHA665752 or/and PI-103 on signaling transduction pathways between parental and PHA665752-resistant SNU-5 xenografts model. The expression level of p-MET, p-AKT, p-ERK, p-S6, p110 α , β, γ, DNA-PK, PTEN, and p53 were analyzed by Western blotting in parental and PHA665752-resistant SNU-5 xenografts after exposing to PHA665752 or/and PI-103. Mean ± SD, n=10. ** P <0.01 vs vehicle group. Abbreviation: SD, standard deviation.

Article Snippet: A selective PI3K p110 α inhibitor PI-103 and MET selective inhibitor PHA665752 were purchased from Selleck Chemicals (Houston, TX, USA).

Techniques: Transduction, Expressing, Western Blot, Standard Deviation