Abstract:

Objective To study the effects of docosahexaenoic acid (DHA) combined with cisplatin on the growth of human gastric cancer xenografts in nude mice, and to explore the mechanism of combined anti-tumor. Methods The models of human gastric cancer transplanted in 28 nude mice were established. The models were randomly divided into control group, DHA group, cisplatin group and combined group, with 7 mice in each group. After 2 weeks of treatment with normal saline, DHA, cisplatin and cisplatin + DHA, the growth of nude mice was observed, the changes of tumor volume and tumor weight were recorded; the morphological changes of cells in each group were observed by HE staining; the apoptosis rate was detected by flow cytometry, the protein expressions of nuclear factor-κB (NF-κB)/p65 and survivin were detected by immunohistochemistry, and the mRNA expressions of NF-κB/p65 and survivin was detected by reverse transcription-PCR. Results Three days after treatment, the tumor volumes in the control group, DHA group, cisplatin group and combined group were (3.13±0.25) cm³, (2.32±0.19)cm³, (1.00±0.08) cm³, (0.50±0.15) cm³, and there was a statistical difference among the four groups (F=314.050, P<0.001). The tumor volumes of the control group, DHA group and cisplatin group were all bigger than that of the combined group (P<0.001; P<0.001; P=0.002). The tumor weights of the control group, DHA group, cisplatin group and combined group were (2.86±0.34) g, (2.14±0.22) g, (1.43±0.18) g, (0.73±0.03) g, and there was a significant difference among the four groups (F=45.570, P<0.001). The tumor weights of the control group, DHA group and cisplatin group were all higher than that of the combined group (P=0.001; P<0.001; P<0.001). HE staining showed that apoptosis of tumor cells was observed in each treatment group, and the combined group was more obvious. The apoptotic rates of the control group, DHA group, cisplatin group and combined group were (3.89±1.03)%, (7.46±0.81)%, (14.85±1.10)%, (24.68±1.17)%, with a significant difference (F=545.620, P<0.001), and the control group, DHA group and cisplatin group were all lower than the combined group (all P<0.001). The relative expression levels of NF-κB/p65 protein in the control group, DHA group, cisplatin group and combined group were 0.389±0.027, 0.312±0.032, 0.258±0.031, 0.163±0.036, with a significant difference (F=78.050, P<0.001), and the control group, DHA group and cisplatin group were all higher than the combined group (P<0.001; P<0.001; P=0.018). The relative expression levels of survivin protein in the control group, DHA group, cisplatin group and combined group were 0.480±0.040, 0.366±0.052, 0.305±0.027, 0.197±0.032, with a significant difference (F=115.135, P<0.001), and the control group, DHA group and cisplatin group were all higher than the combined group (P<0.001; P<0.001; P=0.012). The relative expressions of NF-κB/p65 mRNA in the control group, DHA group, cisplatin group and combined group were 0.902±0.020, 0.780±0.040, 0.560±0.040, 0.350±0.030, with a significant difference (F=1 468.705, P<0.001), and the control group, DHA group and cisplatin group were all higher than the combined group (P<0.001; P<0.001; P=0.026). The relative expressions of survivin mRNA in the control group, DHA group, cisplatin group and combined group were 0.890±0.050, 0.760±0.020, 0.510±0.030, 0.280±0.040, with a significant difference (F=2 099.107, P<0.001), and the control group, DHA group and cisplatin group were all higher than the combined group (P<0.001; P<0.001; P=0.030). Conclusion DHA combined with cisplatin can inhibit the growth of transplanted tumor in nude mice. The mechanism may be related to down regulating the expression of survivin and NF-κB/p65, inducing apoptosis and increasing the sensitivity of chemotherapy drugs.

Key words: Stomach neoplasms, Docosahexaenoic acids, Apoptosis, Survivin, NF-κB/p65