# The impact of thyroid hormone concentration fluctuations on colon cancer proliferation and growth

**Authors:** Fang Ren, Yaqi Zhang, Cancan Hui, Zekai Li, Datong Deng

PMC · DOI: 10.3389/fendo.2025.1576665 · Frontiers in Endocrinology · 2025-07-17

## TL;DR

This study shows that changes in thyroid hormone levels can influence the growth and spread of colon cancer, with lower hormone levels slowing cancer growth and increasing cell death.

## Contribution

The study demonstrates that reducing thyroid hormone levels can inhibit colon cancer proliferation and promote apoptosis in a mouse model.

## Key findings

- Hypothyroidism significantly reduced tumor growth and increased apoptosis in colon cancer cells.
- Hyperthyroidism did not significantly increase tumor growth compared to the control group.
- Ki67 expression was significantly lower in hypothyroid mice compared to control and hyperthyroid groups.

## Abstract

To examine the effects of thyroid hormone (TH) levels on colon cancer progression, HCT-116 colon cancer cells were inoculated into the axillary region of thymus-deficient male BALB/c nude mice. Mild hypothyroidism and hyperthyroidism were then induced to observe tumor growth patterns under different TH conditions.

Following subcutaneous tumor implantation, mice were randomly divided into three groups: hyperthyroid (levothyroxine-treated), hypothyroid (methimazole-treated), and control (saline-treated). Tumor volume and final mass were monitored throughout the study period. Excised tumors were subjected to histological analysis including hematoxylin-eosin (HE) staining, immunofluorescence, and TUNEL assay for apoptosis detection.

In the tumor-bearing experiment conducted with nude mice, the growth curve and tumor weight of the methimazole group exhibited a inhibitory trend compared to the saline group (P<0.05). In the immunofluorescence staining experiment, Ki67 expression was higher in control and hyperthyroid groups than hypothyroid (P<0.01 and P<0.001, respectively), with no significant control-hyperthyroid difference (P>0.05). TUNEL staining results demonstrated no significant presence of TUNEL-positive cells in the subcutaneous tumor tissue of the control group. Additionally, the proportion of TUNEL-positive cells in the subcutaneous tumor tissue of the levothyroxine group was slightly lower than in the control group. (P>0.05), whereas the proportion of TUNEL-positive cells in the methimazole group increased significantly (P<0.0001).

Fluctuations in thyroid hormone levels in the body can affect the proliferation and growth of colon cancer cells. Furthermore, reducing thyroid hormone levels can inhibit the proliferation of colon cancer cells while promoting their apoptosis.

## Linked entities

- **Chemicals:** levothyroxine (PubChem CID 5819), methimazole (PubChem CID 1349907), saline (PubChem CID 5234)
- **Diseases:** colon cancer (MONDO:0002032)

## Full-text entities

- **Genes:** Apc (APC, WNT signaling pathway regulator) [NCBI Gene 11789] {aka CC1, Min, mAPC}, Mki67 (antigen identified by monoclonal antibody Ki 67) [NCBI Gene 17345] {aka D630048A14Rik, Ki-67, Ki67}, Hmga2 (high mobility group AT-hook 2) [NCBI Gene 15364] {aka 9430083A20Rik, HMGI-C, Hmgic, pg, pygmy}, Thrap3 (thyroid hormone receptor associated protein 3) [NCBI Gene 230753] {aka 9330151F09Rik, B230333E16Rik, Trap150}, Bub1 (BUB1, mitotic checkpoint serine/threonine kinase) [NCBI Gene 12235] {aka Bub1a, D2Xrf87}, Cd274 (CD274 antigen) [NCBI Gene 60533] {aka A530045L16Rik, B7h1, Pdcd1l1, Pdcd1lg1, Pdl1}, Braf (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 109880] {aka 9930012E13Rik, B-raf, Braf-2, Braf2, C230098H17, D6Ertd631e}, Kras (Kras proto-oncogene, GTPase) [NCBI Gene 16653] {aka K-Ras, K-Ras 2, K-ras, Ki-ras, Kras-2, Kras2}, Ctnnb1 (catenin beta 1) [NCBI Gene 12387] {aka Bfc, Catnb, Mesc}
- **Diseases:** gastrointestinal tumors (MESH:D005770), hyperthyroid (MESH:D006980), hypothyroid (MESH:D007037), DD (MESH:C536170), thymus (MESH:D013953), Colon cancer (MESH:D015179), Tumor (MESH:D009369)
- **Chemicals:** glycerol (MESH:D005990), ethanol (MESH:D000431), alcohol (MESH:D000438), DAPI (MESH:C007293), paraformaldehyde (MESH:C003043), T3 (MESH:D014284), eosin (MESH:D004801), xylene (MESH:D014992), Hematoxylin (MESH:D006416), paraffin (MESH:D010232), methimazole (MESH:D008713), sugars (MESH:D000073893), nitrogen (MESH:D009584), PBS (MESH:D007854), T4 (MESH:D013974), H2O2 (MESH:D006861), DAB (-)
- **Species:** Ovis aries (domestic sheep, species) [taxon 9940], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** BRAFV600E
- **Cell lines:** HCT-116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291), BALB/c — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0184)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12310445/full.md

## References

20 references — full list in the complete paper: https://tomesphere.com/paper/PMC12310445/full.md

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Source: https://tomesphere.com/paper/PMC12310445