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Topical Area: Diet and Cancer

Diet and Cancer (Poster Session)

(P13-005-23) High Folic Acid Supplementation Reprograms Lung’s mTOR/AMPK-Signaling Glycolytic Lactate Metabolism Associated With Cancer Malignancy Transformation

Sunday, July 23, 2023
11:45 AM – 12:45 PM ET
Location: Poster Board 231

    Presenting Author(s)

  • YC

    Yi-Wen Chen, Master

    Dietitian
    Fu Jen Catholic University Hospital
    New Taipei City, New Taipei, Taiwan (Republic of China)

    • Co-Author(s)

  • SH

    Su-Yu Huang

    Fu Jen Catholic University

  • Wen-Jing Chen, PhD (she/her/hers)

    Assistant Research Fellow
    Cardiovascular and Mitochondrial Related Diseases Research Center/Hualien Tzu Chi Hospital
    Kaohsiung, Kaohsiung, Taiwan (Republic of China)

  • YL

    Yi-Fang Liu, PhD

    Fu Jen Catholic University
    New Taipei City, Taipei, Taiwan (Republic of China)

  • RH

    Rwei-Fen S. Huang


    Fu Jen Catholic University
    New Taipei City, Taipei, Taiwan (Republic of China)

Disclosure(s):
Yi-Wen Chen, Master: No relevant financial relationship(s) with ineligible companies to disclose.
Wen-Jing Chen, PhD: No relevant financial relationship(s) with ineligible companies to disclose.


Objectives: The poor prognosis of patients with lung cancers is mainly due to highly invasion and metastasis. Studies showed that tumor cells underwent glycolysis to accumulate lactate to obtain energy through "Warburg effect", and acidulate the tumor microenvironment. It induced energy metabolic switch to promote invasion and metastasis. Patients with lung cancer were treated with folic acid supplementation (FS) as a nutritional adjuvant therapy during antifolate chemotherapy. Whether high folate may modify the lactate-generating metabolism of malignant lung tumors is unclear. Aims of this study were to investigate effects of FS on lactate and glycolysis metabolism, malignant transformation and its’ working mechanisms.

Methods: The study design includes animal and cell experiment. Six-week-old C57BL/6 male mice were fed with control diet (2 mg/kg folic acid) and folic acid supplementation diet (8 mg/kg folic acid) plus folate supplement water (8 mg/ml folic acid) 14 days prior to the intrapleural injection with 1 × 106 cells/ml Lewis lung cancer cells (LLC) or saline, and the drugs (Rapamycin, Metformin) were injected into the abdominal cavity of each group for 9 days. After 9 days, mice were sacrificed for collecting and analyzing blood and lung tissue. Human lung cells A549 were cultured in control (C) medium (2.2 μM folic acid) or FS medium (50 μM folic acid) for 3 days, and add the drugs (Rapamycin and Metformin) 24 hours of culture on the fourth day. Cells were harvested to explore the bioenergetics metabolism switch.

Results: The results showed that high FS microenvironment increased AMPK and mTOR signaling pathway, up-regulating the expression of HK2, LDH, IRS-1, HIF-1α, GLUT1, MCT1. It induced abnormal glucose metabolism and cellular lactate accumulation to malignant transformation of lung cancers.

Conclusions: In conclusion, the results indicated that high FS microenvironment reprograms mTOR/AMPK-signaling lactate and glycolysis metabolism to promote lung cancer’s malignant transformation.

Funding Sources: National Science and Technology Council, Taiwan, R.O.C.