Effects of Holothurian Glycosaminoglycan on the Sensitivity of Lung Cancer to Chemotherapy

Integr Cancer Ther. 2020 Jan-Dec:19:1534735420911430. doi: 10.1177/1534735420911430.

Abstract

Sea cucumber is a kind of food. Holothurian glycosaminoglycan (hGAG) is extracted from the body wall of the sea cucumber. Administration of hGAG and cisplatin (DDP) together to treat lung cancer was investigated. Lung adenocarcinoma A549 cells were cultured and divided into 4 groups: control group, hGAG 100 µg/mL group, DDP 3 µg/mL group, and hGAG 100 µg/mL + DDP 3 µg/mL group. Cell inhibition and apoptosis was evaluated by CCK8 and Hoechst33258 staining. Cell cycle was tested by Annexin V-FITC/PI (propidium iodide) double-staining and flow cytometry. The expression of mRNA and protein of Bcl-2, Bax, caspase-3, and survivin were detected by reverse transcriptase-polymerase chain reaction and Western blot, respectively. The results showed that hGAG combined with DDP enhanced the inhibitory effect of DDP on A549 lung cells through apoptosis pathway. The mechanism of apoptosis may be related to the reduction of Bcl-2 and survivin, as well as the ascension of Bax and caspase-3. hGAG could promote A549 cell cycle arrest in G1 and G2 phase and improve the DDP chemotherapy effects on A549 cells.

Keywords: Bax; Bcl-2; DDP; caspase-3; chemotherapy; cisplatin; hGAG; holothurian glycosaminoglycan; lung cancer; survivin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung* / drug therapy
  • Adenocarcinoma of Lung* / metabolism
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Drug Synergism
  • Glycosaminoglycans / pharmacology*
  • Holothuria / chemistry*
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Survivin / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents
  • BAX protein, human
  • BIRC5 protein, human
  • Glycosaminoglycans
  • Proto-Oncogene Proteins c-bcl-2
  • Survivin
  • bcl-2-Associated X Protein
  • Caspase 3
  • Cisplatin