J Cancer 2021; 12(2):343-357. doi:10.7150/jca.50500

Research Paper

The Inhibitory Effects of Recombinant Hespintor Combined with Sorafenib on Transplanted Human Hepatoma in Nude Mice, and Transcriptional Regulation of Hespintor Based on RNA-Seq

Yong-Zhi Lun, Jie Sun, Ben Liu, Wen Dong, Ling-Hong Pan, Jian Lin, Jing-Xia Zhang

Key Laboratory of Medical Microecology, Fujian Province University, School of Pharmacy and Medical Technology, Putian University, Putian 351100, China.

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Citation:
Lun YZ, Sun J, Liu B, Dong W, Pan LH, Lin J, Zhang JX. The Inhibitory Effects of Recombinant Hespintor Combined with Sorafenib on Transplanted Human Hepatoma in Nude Mice, and Transcriptional Regulation of Hespintor Based on RNA-Seq. J Cancer 2021; 12(2):343-357. doi:10.7150/jca.50500. Available from https://www.jcancer.org/v12p0343.htm

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Abstract

Objective: As targeted drugs, exogenous serpins could be introduced to patients to restore body balance. This study aimed to observe further the inhibitory effects of recombinant Hespintor (a Kazal-type serpin) combined with Sorafenib on transplanted human hepatoma tumors in nude mice specimens and to explore the possible transcriptional regulation by Hespintor.

Methods: A model of human hepatoma tumors transplanted in nude mice was established, and the medication was administrated to observe the growth of the tumors. Four weeks after the drug administration, the tumors were removed to evaluate the inhibition effects of Hespintor on in-situ tumor growth and liver metastasis. The expression levels of MMP2, MMP9, Bax, Bcl-2, and caspase-3 in the tumor organizations were detected with Western blot. The target genes of the Hespintor were screened based on tissue RNA-Seq, and the regulatory network was constructed.

Results: It was found that the recombinant Hespintor displayed a significant antitumor effect on the subcutaneous growth of MHCC97-H cells. Moreover, the therapeutic effects of the combination therapy were significantly better than those of single therapy. 10 target genes with significantly different expression by Hespintoron tumor tissue were identified. Finally, a visual regulatory networkwas constructed for target mRNA-pathway.

Conclusions: The antitumor effect of Hespintor combined with Sorafenib in treating the subcutaneously implanted hepatocellular carcinoma tumors in nude mice was significant. The possible transcriptional regulation by Hespintor involved multiple signaling pathways, and it was not just the antitumor effect of uPA via its extracellular inhibitions.

Keywords: Hespintor, Serpins, Advanced hepatocellular carcinoma, RNA-Seq, Differentially expressed genes, Reactive oxygen species