Fig 2: ALOX5 overexpression promotes cell growth and protects gastric cancer cells from chemotherapeutic agents‐induced toxicity. (A and B) Analysis of proliferation of AGS and N87 cells after ALOX5 overexpression performed by BrdU labeling. (C and D) Analysis of colony formation of AGS and N87 cells after ALOX5 overexpression. (E and F) Analysis of migration of AGS and N87 cells after ALOX5 overexpression. Analysis of proliferation (G and H) and apoptosis (I and J) after treatment of 5‐FU and cisplatin in ALOX5‐overexpressing AGS and N87 cells. Results are presented as relative to control. Proliferation and apoptosis assays were assessed after 72 h of drug treatment. 5‐FU at 200 nM and cisplatin at 300 nM were used. *p < 0.05, compared to p‐Vector. #p < 0.05, compared to cisplatin or 5‐FU alone

Fig 3: ALOX5 knockdown inhibits gastric cancer and enhances the toxicity of chemotherapeutic agents. Analysis of proliferation (A and B) and apoptosis (C and D) in AGS and N87 cells after ALOX5 knockdown, and in the presence of 5‐FU and cisplatin. ALOX5 knockdown significantly enhances the anti‐proliferative and pro‐apoptotic effects of 5‐FU and cisplatin in gastric cancer cells. 5‐FU at 50 nM and cisplatin at 50 nM were used. Proliferation and apoptosis assays were assessed after 72 h of drug treatment. Results are presented as relative to control. *p < 0.05, compared to control. #p < 0.05, compared to cisplatin or 5‐FU

Fig 4: Alox5 inhibitors suppress gastric cancer and enhance the toxicity of chemotherapeutic agents. (A and B) Proliferation level of AGS and N87 cells after zileuton and AA861 treatment in the presence of 5‐FU and cisplatin, as evaluated by BrdU labeling. (C and D) Proliferation level of AGS and N87 cells after zileuton and AA861 treatment in the presence of 5‐FU and cisplatin, as evaluated by TUNEL assay. Zileuton and AA861 significantly enhance the anti‐proliferative and pro‐apoptotic effects of 5‐FU and cisplatin in gastric cancer cells. 5‐FU at 50 nM and cisplatin at 50 nM were used. Zileuton at 100 μM and 200 μM, AA86 at 30 μM and 60 μM were used in proliferation and apoptosis assays, respectively. Proliferation and apoptosis assays were assessed after 72 h of drug treatment. *p < 0.05, compared to control. #p < 0.05, compared to cisplatin or 5‐FU

Fig 5: Alox5‐5‐HETE axis is upregulated in gastric cancer tissues. (A) Scatter plot of Alox5 protein level in paired normal and tumor tissues obtained from 52 patients with gastric tumor. (B) Representative immunohistochemistry analysis of normal and tumor gastric tissues from patient#23 performed by Alox5 staining. (C) Scatter plot of 5‐HETE level in paired normal and tumor tissues obtained from 52 patients with gastric tumor. Alox5 and 5‐HETE were assessed using tissue homogenates and quantified using ELISA assay. (D) Relative tumor/normal ratio value of Alox5 and 5‐HETE levels in individual gastric cancer patients. Alox5 or 5‐HETE level in normal tissues were set as 1 (indicated by a red line)