Functional vinorelbine plus schisandrin B liposomes destroying tumor metastasis in treatment of gastric cancer

Abstract

Gastric cancer is one of the leading causes of cancer-related death worldwide with a poor prognosis. Gastric cancer is usually treated with surgery and chemotherapy, accompanied by a high rate of metastasis and recurrence. In this paper, R₈ (RRRRRRRR) modified vinorelbine plus schisandrin B liposomes had been successfully constructed for treating gastric cancer. In the liposomes, R₈ was used to enhance the intracellular uptake, schisandrin B was incorporated into liposomes for inhibiting tumor cells metastasis, and vinorelbine was encapsulated into liposomes as antitumor drugs. Studies were performed on BGC-823 cells in vitro and were verified in the BGC-823 cell xenografts nude mice in vivo. Results in vitro demonstrated that the targeting liposomes could induce BGC-823 cells apoptosis, inhibit the metastasis of tumor cells, and increase targeting effects to tumor cells. Meanwhile, action mechanism studies showed that the targeting liposomes could down-regulate VEGF, VE-Cad, HIF-1a, PI3K, MMP-2, and FAK to inhibit tumor metastasis. In vivo results exhibited that the targeting liposomes displayed an obvious antitumor efficacy by accumulating selectively in tumor site and induce tumor cell apoptosis. Hence, R₈ modified vinorelbine plus schisandrin B liposomes might provide a safe and efficient therapy strategy for gastric cancer.

Keywords:

• Gastric cancer
• vinorelbine
• schisandrin B
• targeted liposomes
• R₈ peptide

Disclosure statement

All authors declare that there are no conflicts of interest.

Additional information

Funding

This work was supported by the Research Center for Engineering (Technology) of Traditional Chinese Medicine Microemulsions and New Biological Preparations, Shanxi University of Chinese Medicine [2019WSZX01], the National Natural Science Foundation of China [No. 81903813], the Shanxi Province Science Foundation for Youths [No. 201801D221434], and the Scientific and Technological Innovation Ability Cultivation Project of Shanxi University of Chinese Medicine [2019-PY-140].