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. Author manuscript; available in PMC: 2019 Nov 26.
Published in final edited form as: Sci Transl Med. 2019 Mar 13;11(483):eaaq1238. doi: 10.1126/scitranslmed.aaq1238

Fig. 4. Lung cancer cells and tumors with high ZEB1 are resistant to MEK inhibition.

Fig. 4.

(A and B) In vitro cell survival response after 72-hour selumetinib (AZD6244) treatment in a panel of epithelial and mesenchymal (A) human and (B) murine RAS mutant lung cancer cell lines.

(C) H&E, IL17RD, p-ERK, ZEB1, E-cadherin, and vimentin IHC stains of primary tumor tissues generated by subcutaneous injection of epithelial 393P and mesenchymal 344SQ murine lung cancer cell lines in syngeneic wild-type mice (n=8 tumors per group). Scale bars, 100 μm. Inset scale bars, 20 μm.

(D) Left: In vivo volume measurements at the indicated time points for 393P and 344SQ subcutaneous tumors in syngeneic wild-type mice after daily treatment with 25 mg/kg AZD6244 MEK inhibitor or vehicle control. Treatment start time denoted by green arrow, endpoint denoted by red arrows, and resistant tumors denoted by purple arrow. Treatment performed in experimental duplicate with 4 to 5 mice per replicate in each treatment group. Sample size is as indicated in the middle graph. Tumor volume data plotted as the mean and standard deviation. Purple data points represent 393P tumors that were initially responsive to MEK inhibition and developed resistance over time. Middle: Tumor volume measurements at Week 7 (at the endpoint, after 4 weeks of AZD6244 treatment). Right: Quantification of lung metastatic surface nodules in the indicated experimental groups at Week 7 of the experiment or at Week 12 in 393P tumors that developed resistance to AZD6244 (393P AZD-R). *: p<0.05, **: p<0.01.

(E) Stains for the indicated markers in 393P tumors in mice that received vehicle or AZD6244 until Week 7 of the experiment in (D) (top and middle panels), or in tumors that developed resistance to AZD6244 (393P AZD-R) at Week 12 of the experiment in (D) (bottom panel). Scale bars, 50 μm. Inset scale bars, 20 μm. Images are representative of n=5 tissues per group.