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Original Research

Chloroquine Combined with Imatinib Overcomes Imatinib Resistance in Gastrointestinal Stromal Tumors by Inhibiting Autophagy via the MAPK/ERK Pathway

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Pages 6433-6441 | Published online: 02 Jul 2020

Figures & data

Figure 1 (A) Effect of imatinib on drug sensitivity of GIST882 cell line. (B) Effect of imatinib on drug sensitivity of GIST882-ir cell line. (C) Effect of imatinib and chloroquine on apoptosis of GIST882-ir cell line (after 48h). (D) The effects of Imatinib and Chloroquine on cell viability of GIST882-ir strains after 8h, 24h and 48h. (E) The two essential proliferative intracellular signaling pathways, PI3K/Akt/mTOR and MAPK. (F) Five group Western blot results. 1. GIST882, 2. GIST882-ir, 3. GIST882-ir +im, 4. GIST882-ir +CQ, 5. GIST882-ir +im+CQ.

Figure 1 (A) Effect of imatinib on drug sensitivity of GIST882 cell line. (B) Effect of imatinib on drug sensitivity of GIST882-ir cell line. (C) Effect of imatinib and chloroquine on apoptosis of GIST882-ir cell line (after 48h). (D) The effects of Imatinib and Chloroquine on cell viability of GIST882-ir strains after 8h, 24h and 48h. (E) The two essential proliferative intracellular signaling pathways, PI3K/Akt/mTOR and MAPK. (F) Five group Western blot results. 1. GIST882, 2. GIST882-ir, 3. GIST882-ir +im, 4. GIST882-ir +CQ, 5. GIST882-ir +im+CQ.

Figure 2 (A) Effect on tumor volume. (B) The immunohistochemical detection of Beclin 1 protein expression in rat tumor tissue. (C) The immunohistochemical detection of caspase 3 protein expression in rat tumor tissue. (D) immunohistochemical detection of caspase 7 protein expression in rat tumor tissue.

Abbreviations: CK, normal control group; im-r, imatinib-resistant group; im, imatinib-resistant cells + imatinib; CQ, imatinib-resistant cells + chloroquine; im+ CQ, imatinib-resistant cells + imatinib + chloroquine.

Figure 2 (A) Effect on tumor volume. (B) The immunohistochemical detection of Beclin 1 protein expression in rat tumor tissue. (C) The immunohistochemical detection of caspase 3 protein expression in rat tumor tissue. (D) immunohistochemical detection of caspase 7 protein expression in rat tumor tissue.Abbreviations: CK, normal control group; im-r, imatinib-resistant group; im, imatinib-resistant cells + imatinib; CQ, imatinib-resistant cells + chloroquine; im+ CQ, imatinib-resistant cells + imatinib + chloroquine.

Figure 3 (A) Changes of body weight in mice. (B) Beclin1 expression in tumor tissue detected by immunohistochemistry. (C) Caspase-3 expression in tumor tissue detected by immunohistochemistry. (D) Caspase-7 expression in tumor tissue detected by immunohistochemistry.

Figure 3 (A) Changes of body weight in mice. (B) Beclin1 expression in tumor tissue detected by immunohistochemistry. (C) Caspase-3 expression in tumor tissue detected by immunohistochemistry. (D) Caspase-7 expression in tumor tissue detected by immunohistochemistry.

Figure 4 (A) LC3II/I protein expression. Compared with the normal group (CK group). Imatinib-r group: imatinib-resistant group. Imatinib-r group vs. CK group, *p<0.05, **p<0.01; each drug administration group vs. Imatinib-r group, #p<0.05, ##p<0.01; Imatinib+CQ group vs. Imatinib group, and p<0.05, and p<0.01. (B) Analysis of KIT and ERK protein expression and phosphorylation level.

Figure 4 (A) LC3II/I protein expression. Compared with the normal group (CK group). Imatinib-r group: imatinib-resistant group. Imatinib-r group vs. CK group, *p<0.05, **p<0.01; each drug administration group vs. Imatinib-r group, #p<0.05, ##p<0.01; Imatinib+CQ group vs. Imatinib group, and p<0.05, and p<0.01. (B) Analysis of KIT and ERK protein expression and phosphorylation level.