Abstract:

Objective To explore the inhibitory effect and mechanism of photocarcinorin (PSD-007) photodynamic therapy (PDT) on human nasopharyngeal carcinoma transplanted tumors in nude mice. MethodsA total of 50 transplanted tumor nude mice models of human nasopharyngeal carcinoma were established and randomly divided into 5 groups: control group (group A), simple PSD-007 group (group B), simple light group (group C), local injection of PSD-007 + light group (group D), intraperitoneal injection of PSD-007 + light group (group E) using the method of random number table, 10 mice in each group. After 7 days of treatment, the tumor mass and tumor volume of nude mice in each group were measured and the tumor inhibition rate was calculated. HE staining was used to detect the histopathological changes of tumors in nude mice. Western blotting was used to detect the expressions of autophagy-related gene Beclin 1, microtubules associated protein 1 light chain 3-β (LC3) and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway related proteins. Real-time fluorescent quantitative PCR was used to detect LC3, Beclin 1 mRNA expressions in tumor tissues. Results After treatment, the tumor mass of nude mice bearing human nasopharyngeal carcinoma in group A, B, C, D and E were (2.05±0.18) g, (2.02±0.20) g, (2.04±0.15) g, (0.43±0.11) g and (0.94±0.12) g, and the tumor volumes were (1.11±0.13) cm ³, (1.18±0.16) cm ³, (1.13±0.14) cm ³, (0.51±0.07) cm ³ and (0.65±0.10) cm ³, and there were statistically significant differences among the 5 groups (F=236.749, P<0.001; F=62.418, P<0.001). Compared with group A, B and C, the tumor mass and tumor volumes of nude mice in group D and E were significantly reduced, and there were statistically significant differences (all P<0.001); compared with group E, the tumor mass and tumor volume of nude mice in group D were significantly reduced (P<0.001; P=0.023). The tumor inhibition rates of group B, C, D and E were (1.07±0.11)%, (0.55±0.06)%, (79.11±0.06)% and (54.05±0.08)%, with a statistically significant difference (F=235.987, P<0.001), compared with group B, C and E, group D had the most obvious tumor suppressing effect (all P<0.05). HE staining results showed that compared with group A, B and C, group D and E had larger tumor necrosis areas, more inflammatory cell infiltration, more vacuolar degeneration, and obvious nuclear shrinkage. The tumor necrosis degree in group D was higher than that in group E. The relative expressions of PI3K protein of group A, B, C, D and E were 1.01±0.06, 1.00±0.05, 1.01±0.05, 0.23±0.02, 0.48±0.04, p-Akt/Akt protein relative expressions were 0.66±0.06, 0.65±0.05, 0.64±0.05, 0.06±0.02, 0.17±0.02, p-mTOR/mTOR protein relative expressions were 1.06±0.06, 1.01±0.06, 1.01±0.06, 0.30±0.02, 0.45±0.04. The protein relative expression ratios of LC3 Ⅱ/LC3 Ⅰ were 0.85±0.05, 0.83±0.05, 0.83±0.06, 0.22±0.02, 0.41±0.04, and Beclin 1 protein relative expressions were 0.66±0.06, 0.64±0.05, 0.64±0.06, 1.67±0.07, 1.02±0.05, LC3 mRNA relative expressions were 0.98±0.29, 0.92±0.25, 1.02±0.26, 3.76±0.28, 2.38±0.28, and Beclin 1 mRNA relative expressions of were 1.11±0.40, 1.19±0.29, 1.16±0.24, 6.84±0.54, 2.94±0.48. There were statistically significant differences (F=190.160, P<0.001; F=160.014, P<0.001; F=160.183, P<0.001; F=119.964, P<0.001; F=186.257, P<0.001; F=211.089, P<0.001; F=374.835, P<0.001). Compared with group A, B and C, PI3K, p-Akt/Akt and p-mTOR/mTOR protein relative expression levels and protein relative expression ratios of LC3 Ⅱ/LC3 Ⅰ in nude mice tumors of group D and E were significantly reduced, and LC3 mRNA, Beclin 1 protein and mRNA relative expression levels were significantly increased, with statistically significant differences (all P<0.001); PI3K, p-Akt/Akt and p-mTOR/mTOR protein relative expression levels and protein relative expression ratio of LC3 Ⅱ/LC3 Ⅰ in nude mice tumors of group E were significantly higher than those of group D, while Beclin 1 protein relative expression levels, LC3 and Beclin 1 mRNA relative expression levels were reduced (all P<0.05). Conclusion PSD-007 PDT has an inhibitory effect on human nasopharyngeal carcinoma transplanted tumors in nude mice, which may be related to the inhibition of PI3K/Akt/mTOR signaling pathway activation and the promotion of autophagy. Compared with intraperitoneal injection, local injection of PSD-007 PDT is more effective.

Key words: Nasopharyngeal neoplasms, Photochemotherapy, Phosphatidylinositol 3-kinase, Photocarcinorin, Protein kinase B