ICAM2 loss drives 5-fluorouracil resistance via TGF-β/Smad/SP1/PTN-dependent apoptosis evasion and macrophage remodeling in gastric cancer

Figure 6 Targeting TGF-β/Smad signaling overcomes 5-fluorouracil resistance in gastric cancer with low intercellular adhesion molecule 2 expression. A: Representative tumor images and tumor volume changes in mice bearing MGC803 xenografts treated with vector + DMSO, intercellular adhesion molecule 2 (ICAM2)-OE + DMSO, vector + 5-fluorouracil (5-FU), and ICAM2-OE + 5-FU. Tumor weights were measured on day 22 (n = 6/group); B: Immunohistochemistry (IHC) staining for ICAM2, Ki-67, pleiotrophin (PTN), and cleaved caspase-3, along with TUNEL staining in tumors from the indicated groups; C: Representative tumor images and tumor volume changes in mice bearing MKN45 xenografts treated with Shcon + DMSO, ICAM2-sh1 + DMSO, Shcon + 5-FU, ICAM2-sh1 + 5-FU, and ICAM2-sh1 + 5-FU + LY2157299. Tumor weights were measured on day 22 (n = 5/group); D: IHC staining for ICAM2, Ki-67, PTN, and cleaved caspase-3, along with TUNEL staining in tumors from the indicated groups. ^aP < 0.05; ^bP < 0.01; ^cP < 0.001. 5-FU: 5-fluorouracil; ICAM2: Intercellular adhesion molecule 2; PTN: Pleiotrophin.