Sequential IVIM-Parametric as a Potential Image Biomarker in Evaluating the Radiosensitivity of Human Nasopharyngeal Carcinoma Xenografts

BACKGROUND AND PURPOSEIntravoxel incoherent motion (IVIM) is a considerable functional MR sequence in evaluated the tumor’s response to chemo-radiotherapy. Our aim was to investigate the sequential IVIM parametric in assessing the dynamic changes of histopathological features on nasopharyngeal carcinoma (NPC) xenografts after receiving the fractional radiations.EXPERIMENTAL APPROACH: Sixty BALB/c-nu nude mice were transplanted with NPC cell lines of CNE-1 and CNE-2 to raise xenografts which further received the fractional radiations. On 3.0T MR system, IVIM (14 b-factors: 0~1000 s/mm2) was performed on xegnorafts after radiations. IVIM-parametric of D, f and D* accompanied with the cellularity and necrosis proportion of NPC xenografts were calculated and analyzed respectively.KEY RESULTSNPC xenografts exhibited a larger D and necrosis proportion coupled with a smaller D*, f and cellularity after fractional radiations, and CNE-2 xenografts presented greater changes than CNE-1 xenografts (all P<0.01). Parametric D and f correlated negatively (r=-0.824, P<0.001) while D* correlated positively with f (r=0.758, P<0.001) and D (r=0.625, P=0.042). Moreover, D correlated negatively with cellularity (rs=-0.861, P<0.001) and positively with necrosis proportion (rs=0.952, P<0.001), f behaved a positive correlation with cellularity (rs=0.627, P<0.001) and negative with necrosis proportion (rs=-0.649, P<0.001). CONCLUSIONS AND IMPLICATIONS: Sequential parametric derived from IVIM are valuable in characterizing the dynamic changes in histopathological features of NPC xenografts and can be utilized as a potential image biomarker for non-invasive assessment of tumor’s radiosensitivity.

Anti-Cancer Properties of Ginkgolic Acids in Human Nasopharyngeal Carcinoma CNE-2Z Cells via Inhibition of Heat Shock Protein 90

Ginkgo biloba L. has been used in traditional Chinese medicine (TCM) for thousands of years. However, the anti-cancer properties of ginkgolic acids (GAS) isolated from G. biloba have not been investigated in human nasopharyngeal carcinoma cells. In this study, GAS exhibited an inhibitory effect on the ATPase activity of heat shock protein 90 (Hsp90) and anti-proliferative activities against four human cancer cell lines, with IC50 values ranging from 14.91 to 23.81 μg·mL−1. In vivo experiments confirmed that GAS inhibited tumor growth in CNE-2Z cell-xenografted nude mice with low hepatotoxicity. We further demonstrated that GAS suppressed migration and invasion and induced the apoptosis of CNE-2Z cells by inducing the degradation of Hsp90 client proteins (MMP-2, MMP-9, Her-2, c-Raf, Akt, and Bcl-2). Together, GAS are new Hsp90 inhibitors by binding to Hsp90 (hydrogen bond and hydrophobic interaction). Thus, GAS from G. biloba might represent promising Hsp90 inhibitors for the development of anti-nasopharyngeal carcinoma agents.

Morusin Suppresses Cancer Cell Invasion and MMP-2 Expression through ERK Signaling in Human Nasopharyngeal Carcinoma

The most important cause of treatment failure of nasopharyngeal carcinoma (NPC) patients is metastasis, including regional lymph nodes or distant metastasis, resulting in a poor prognosis and challenges for treatment. In the present study, we investigated the in vitro anti- tumoral properties of morusin on human nasopharyngeal carcinoma HONE-1, NPC-39, and NPC-BM cells. Our study revealed that morusin suppressed the migration and invasion abilities of the three NPC cells. Gelatin zymography assay and Western blotting demonstrated that the enzyme activity and the level of matrix metalloproteinases-2 (MMP-2) protein were downregulated by the treatment of morusin. Mitogen-activated protein kinase proteins were examined to identify the signaling pathway, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of morusin. In summary, our data showed that morusin inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by downregulating the ERK1/2 signaling pathway, suggesting that morusin may be a potential candidate for chemoprevention or adjuvant therapy of NPC.