Deregulation of EGFR/PI3K and activation of PTEN by photodynamic therapy combined with carboplatin in human anaplastic thyroid cancer cells and xenograft tumors in nude mice
Abstract
Phosphatidylinositol-3-kinase (PI3K) is one of the major activated pathways involved in the progression of anaplastic thyroid cancer. The activated PI3K pathway starts from the overexpression of epidermal growth-factor receptor (EGFR) which plays a key role in cancer development and metastasis. However, a protein, PTEN negatively regulates the PI3K pathway. Here we studied the possibility of using a combination of conventional chemotherapy and photodynamic therapy to inhibit the growth of human anaplastic thyroid cancer in vitro and in vivo. Carboplatin (CBDCA) and radachlorin-photodynamic therapy (PDT) were used for the combination treatment of human anaplastic thyroid cancer cells FRO and tumor xenograft in athymic mice. Confocal microscopic and flow cytometric observations showed that cell death was mainly through an enhanced apoptosis with the combination of CBDCA and PDT. Generation of reactive oxygen species and dysfunction of mitochondrial membranes suggested that the enhanced apoptosis was achieved through the mitochondrial cell death pathway. This was confirmed by Western blot analysis of caspase 3, 9 expressions. Further analysis showed that the combination of CBDCA and PDT inhibited the expression of EGFR and PI3K with higher efficacy. PTEN also was activated more in this combination group. This suggests a combination of CBDCA and PDT modulates EGFR and PI3K as well as activates PTEN to inhibit tumor growth and induce apoptosis with an enhanced efficacy in anaplast…
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Photodynamic therapy, used alone or in combination with chemotherapy, has given promising results in preclinical studies for thyroid cancer.
“Photodynamic therapy is a hope, which, used alone or in combination with previously used chemotherapy, gave promising results in preclinical studies. [6-10].”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
EGFR expression was unchanged with carboplatin therapy and slightly decreased with PDT and combination therapy.
“As for EGFR expression, it was unchanged in the case of carboplatin therapy and slightly decreased in the case of PDT and combination therapy.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
The most commonly used photosensitizers in PDT for thyroid cancers include hypericin, porphyrin, photophrin, radachlorin, and 5-aminolevulinic acid (ALA).
“The most commonly used PS in PDT for the treatment of thyroid cancers include hypericin, porphyrin, photophrin, radachlorin, and 5-aminolevulinic acid (ALA). [8-10,14,32]”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
Mitochondrial membrane potential was moderately decreased after carboplatin (14.5%), noticeably decreased in PDT (49.3%), and significantly decreased in combination therapy (80.6%).
“Mitochondrial membrane potential was moderately decreased after the treatment of cell lines with carboplatin (14.5%), a noticeable decrease in PDT (49.3%), and in the combination therapy this decrease was significant (80.6%).”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
Cytochrome c expression increased with PDT and then increased slightly in combination therapy.
“Cytochrome c expression, which is a marker of mitochondrial membrane depolarization and cell apoptosis associated with mitochondrial dysfunction, increased with PDT and then increased slightly in combination therapy.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
A relationship between PDT and combination therapy and expression of caspase-3 and caspase-9 was demonstrated; their activity increased in both cases, with a greater increase in combination therapy.
“A relationship between PDT and combination therapy and the expression of proteins involved in the mitochondrial pathway, caspase3 and caspase-9, was also demonstrated. Their activity increased in both cases, with a greater increase in combination therapy.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
Cell motility decreased most in combination therapy; in single therapies, the decrease was greater with PDT than with carboplatin.
“Cell motility also decreased most in the case of combination therapy, and in the case of single therapies, this decrease was greater in the case of PDT than carboplatin.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
In PDT, the number of cells with increased ROS was 81.6%, compared to 87.1% in combination therapy.
“It was shown that in the case of PDT, the number of cells with increased ROS was 81.6%, compared to the combination therapy, where it was 87.1%.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
Combination therapy was the only one to have a significant effect on the change in PI3K and PTEN expression.
“Combination therapy was the only one to have a significant effect on the change in PI3K and PTEN expression.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
The combination of carboplatin and PDT with radachlorin completely inhibited the cancer cell line at concentrations of 0.05 mg/ml carboplatin and 3.12 ng/ml radachlorin.
“The combination of carboplatin and PDT with radachlorin completely inhibited the cancer cell line at concentrations of 0.05 mg/ml carboplatin and 3.12 ng/ml radachlorin.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
The number of live cells decreased in direct proportion to the concentration of carboplatin.
“the number of live cells decreased in direct proportion to the concentration of carboplatin.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
Combined therapy was characterized by apoptotic cells with irregular outlines, disruption of nuclear membranes, and chromatin condensation in histopathological examination.
“The combined therapy was characterized by apoptotic cells with irregular outlines, disruption of nuclear membranes, chromatin condensation in histopathological examination.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
In the combination of PDT with radachlorin and carboplatin, the percentage of live cells decreased to about 30%, compared to about 89% with carboplatin alone and about 80% with PDT alone.
“In the combination of PDT with radachlorin as PS and carboplatin, the percentage of live cells decreased very significantly, to about 30%, compared to the control groups using only carboplatin (about 89%) or only PDT with radachlorin (about 80%).”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
In PTEN expression, PDT showed no change, carboplatin a slight one, and combination therapy a significant one.
“In the case of PTEN expression, PDT showed no change, carboplatin a slight one, and combination therapy a significant one.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
Combination therapy significantly decreased PI3K expression, with no significant decrease in single therapies.
“Combination therapy has a significant effect on the decrease in PI3K expression, with no significant decrease in single therapies.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
PDT may inhibit cancer tissue development by reducing expression of EGFR and PI3K pathways.
“PDT may also have an impact on the inhibition of cancer tissue development by reducing the expression of EGFR and PI3K pathways.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
After 7 days, tumor volume was comparable in each of the 3 treatment groups, but inhibited compared to the control group.
“After 7 days, tumor volume was comparable in each of the 3 treatment groups, but inhibited compared to the control group.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
The therapeutic effect of combined carboplatin and PDT with radachlorin is due to effects on the mitochondrial pathway and the EGFR-PI3K pathway.
“The above reports confirm that the therapeutic effect of combined carboplatin and PDT with radachlorin is due to the effect on the mitochondrial pathway and the EGFR-PI3K pathway.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
After 14 days, the decrease in tumor volume was most pronounced in combination therapy, less with PDT, least with carboplatin, but still significant compared to control.
“After 14 days, the decrease in tumor volume was most pronounced in the group of tumors treated with combination therapy, less pronounced with PDT, and least in the group using carboplatin, but the decrease was still significant compared to the control group.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
PDT can increase internalization of chemotherapy drugs, which may be helpful in chemotherapy resistance resulting from reduced endocytosis of tumor cells.
“In addition, PDT can increase the internalization of chemotherapy drugs, which may be helpful in chemotherapy resistance, which results from reduced endocytosis of the tumor cell.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
The changes were particularly marked in higher concentrations of the photosensitizer or in combination with sulforaphene, carboplatin, or genistein.
“The changes were particularly marked in higher concentrations of the photosensitizer or in combination with sulforaphene, carboplatin, or genistein.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
In tumors treated with combination therapy, significantly increased expression of caspase-3, caspase-9, and PTEN, decreased expression of EGFR and PI3K, and proteolytic cleavage to active PARP were observed compared to single therapies.
“Additionally, in the case of tumors treated with combination therapy, significantly increased expression of caspase-3, caspase-9, and PTEN proteins, decreased expression of EGFR and PI3K, and proteolytic cleavage to the active form of poly(ADP-rubose) polymerase (PARP) were observed compared to tumors treated with single therapies.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [8]
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Photodynamic Therapy for Thyroid Cancer
Inglot, J., Strzelczyk, J. K., Bartusik-Aebisher, D., & Aebisher, D. (2025) · BioMed · doi:10.3390/biomed5010008 · Cited by 2 · see citing works
- Authors
- Biswas, R., Mondal, A., & Ahn, J.-C.
- Affiliations
- Dankook University (KR)
- Corresponding author
- Ahn, Jin-Chul
- Venue
- Journal of Photochemistry and Photobiology B: Biology
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 148
- Pages
- 118-127
- ISSN
- 1011-1344 (ISSN-L)
- OpenAlex
- W2006425236
- Cited by
- 21
- References
- 0
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 1 · 2018: 3 · 2017: 2 · 2016: 3
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Photochemistry and Photobiology B Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- anaplastic thyroid carcinoma, photodynamic therapy, carboplatin, EGFR, PI3K signaling, combination chemotherapy, apoptosis, mitochondrial apoptosis, reactive oxygen species, caspase-3, caspase-9, Radachlorin, tumor xenografts
- MeSH terms
- Animals, Cell Movement, Drug Combinations, Drug Therapy, Combination, Female, Humans, Lasers, Mice, Nude, Photochemotherapy, Porphyrins, Transplantation, Heterologous, Carboplatin, Apoptosis, Reactive Oxygen Species, Phosphatidylinositol 3-Kinases, Cell Line, Tumor, PTEN Phosphohydrolase, Mice, Membrane Potential, Mitochondrial, Caspase 3, Thyroid Carcinoma, Anaplastic, ErbB Receptors
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