Expression of the First Recombinant Anti-Tumoral Snake Venom Kunitz-Type Serine Protease Inhibitor

被引：10

作者：

Morjen, Maram ^{[1
]}

Moslah, Wassim ^{[1
]}

Touihri-Baraketi, Imen ^{[2
]}

Srairi-Abid, Najet ^{[1
]}

Luis, Jose ^{[3
]}

Marrakchi, Naziha ^{[1
,4
]}

Jebali, Jed ^{[1
]}

机构：

[1] Univ Tunis El Manar, Pasteur Inst Tunis, Lab Biomol Venoms & Theranost Applicat, LR20IPT01, Tunis 1002, Tunisia

[2] Inst Natl Rech & Anal Phys Chim INRAP, Lab Subst Nat, Sidi Thabet 2020, Ariana, Tunisia

[3] Univ Aix Marseille, Inst Neuro Physiopathol INP, CNRS, UMR 7051, 27 Bd Jean Moulin, F-13385 Marseille, France

[4] Univ Tunis El Manar, Med Sch Tunis, 15 Djebel Lakhdhar,St La Rabta, Tunis 1007, Tunisia

来源：

TOXINS | 2022年 / 14卷 / 03期

关键词：

snake venom; Kunitz-type serine protease inhibitor; recombinant PIVL; tumorogenesis; DENDROTOXIN-K; CELL-ADHESION; MIGRATION; CLONING; PIVL;

D O I：

10.3390/toxins14030170

中图分类号：

TS2 [食品工业];

学科分类号：

0832 ;

摘要：

PIVL is a Kunitz-type serine protease inhibitor that was previously characterized from Tunisian snake venom, Macrovipera lebetina transmediterranea. It reduced glioblastoma cells' development and significantly blocked angiogenesis in in-vitro and ex-vivo models. PIVL exerted these effects by interfering with alpha v beta 3 integrin. In order to produce a biological active recombinant, the cDNA cloning and expression of PIVL was performed in Escherichia coli (BL21)-DE3 cells using pET-22b (+) vector. The recombinant PIVL protein (rPIVL) was purified by nickel affinity chromatography and has recognized monoclonal anti-His antibody. Functionally, rPIVL exhibited potent anti-tumor cell effects as well as anti-angiogenesis properties. Interestingly, we found that both native PIVL (nPIVL) and rPIVL modulated PI3/AKT and MAPK signaling pathways. In all, our results showed that we have successfully expressed the first active anti-oncogenic snake venom Kunitz-type protease inhibitor that can be a potential therapeutic drug against glioblastoma, in its native or recombinant form.

引用

页数：12