2. Academic Validation
  3. Tacrolimus, a rapamycin target protein inhibitor, exerts anti-cystic echinococcosis effects both in vitro and in vivo

Tacrolimus, a rapamycin target protein inhibitor, exerts anti-cystic echinococcosis effects both in vitro and in vivo

  • Acta Trop. 2020 Dec;212:105708. doi: 10.1016/j.actatropica.2020.105708.
Muzhabaier Muhedier 1,  Jintian Li 2,  Hui Liu 3,  Guizhi Ma 4,  Kuerbannisha Amahong 3,  Renyong Lin 5,  Guodong Lü 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, China; Xinjiang Key Laboratory of Echinococcosis, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China; Kashi maternal and child health care hospital, Kashi, Xinjiang, China.
  • 2 State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, China; Xinjiang Key Laboratory of Echinococcosis, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China; College of pharmacy, Xinjiang Medical University, Urumqi, Xinjiang, China.
  • 3 State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, China; Xinjiang Key Laboratory of Echinococcosis, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
  • 4 College of pharmacy, Xinjiang Medical University, Urumqi, Xinjiang, China.
  • 5 State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, China; Xinjiang Key Laboratory of Echinococcosis, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. Electronic address: [email protected].
  • 6 State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, China; Xinjiang Key Laboratory of Echinococcosis, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China; College of pharmacy, Xinjiang Medical University, Urumqi, Xinjiang, China. Electronic address: [email protected].
PMID: 32956634 DOI: 10.1016/j.actatropica.2020.105708
Abstract

In view of a growing need for new treatment options for human cystic echinococcosis (CE), we aimed to investigate the efficacy of mTOR pathway inhibitors against CE in vitro and in vivo. Among the seven mTOR inhibitors evaluated, tacrolimus (TAC) showed significant dose- and time-dependent killing of cultured protoscoleces and cysts in vitro. Notably, the oral administration of TAC (4 mg/kg/day) to CE mice model highly effectively reduced both the weight and number of parasitic cysts. Transmission electron microscopy revealed that TAC destroys the ultrastructure of cysts, both in vitro and in vivo. Furthermore, TAC had no significant effect on blood glucose, body weight, liver, or kidney functions in mice. We further observed that the ATP levels and glucose content of cysts reduced upon TAC treatment, indicating that inhibiting mTORC1 activity possibly affects glucose metabolism in the cysts of mice. Based on our experimental data, TAC emerged as a promising anti-cyst drug that efficiently inhibits the growth of cysts.

Keywords

Anti-cystic echinococcosis; Cystic echinococcosis; Tacrolimus; mTOR inhibitors.

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