Efficacy of Multiple Low-dose Photodynamic TMPYP4 Therapy on Cervical Cancer Tumour Growth in Nude Mice

Abstract

Objective: Photodynamic therapy (PDT) is an emerging therapeutic procedure suitable for the treatment of cervical cancer. However, the side effects of PDT are severe, including skin ulceration, so we designed an experiment to examine the effects of multiple low-dose photodynamic therapy of 5, 10, 15, 20-tetrakis(1-methylpyridinium-4-yl) porphyrin (Tmpyp4) on tumour growth by utilizing a model in nude mice implanted with Hela cervical cancer cells. Materials and Methods: Female BALB/c nude mice (aged 5-6 weeks, weighing 18-20 g) were used. Hela cervical cancer cells were injected subcutaneously (1×10 7 cells/200 μL). Ten days after injection, the mice were divided into three groups (n=6), the A group of controls without any treatment, the B group receiving a single-treatment with Tmpyp4 (10 mg/kg, intratumor injection) and irradiation (blue laser, 108 J/cm 2 ), and the C group given three-treatments with Tmpyp4 (10 mg/ kg, intratumor injection) and irradiation at intervals of two days. After starting treatment, tumours were measured every two days, to assess growth. At 2 weeks after the last treatment of C group, tumour tissue and organs were collected from each mouse to evaluate tumor histology and organ damage. Results: Tumour growth in C group was significantly inhibited compared with A and B groups (P <0.05), without any injury to the skin and internal organs. Conclusion: Our novel findings demonstrated that multiple low-dose photodynamic therapy of Tmpyp4 could inhibit cervical cancer growth significantly with no apparent side effects.

TMPYP4 exerted antitumor effects in human cervical cancer cells through activation of p38 mitogen-activated protein kinase

“…Through directly interaction with telomeres, TMPyP4 can rapidly evoke antiproliferative effects [12]. In vivo, after intratumor injection of 10 mg/kg TMPyP4 for 10 days, cervical tumor growth in nude mice was significantly inhibited without any injury to the skin and internal organs [13]. Therefore, in this study, we used this agent for investigation in cultured human cervical cancer cells to further evaluate its antitumor effects and underlying mechanism.…”

Hiporfin‐Mediated Photodynamic Therapy in Preclinical Treatment of Osteosarcoma

“…Furthermore, we detected skin ulcers in our animal models. To prevent skin ulcers after PDT, one study recently used low concentrations of photosensitizer with multiple irradiation . However, due to the specificity of osteosarcoma, we cannot only use irradiation to eliminate the solid tumor that is localized deep inside the skin.…”

TMPyP4, a Stabilizer of Nucleic Acid Secondary Structure, Is a Novel Acetylcholinesterase Inhibitor

“…To establish whether TMPyP4 can alter Th transcription levels in vivo , adult male and female mice (3–12 months of age) were administered saline or 10mg/kg of either TMPyP2 or TMPyP4 by intraperitoneal injection twice daily for 5 days. This low dosage was similar to those used in photosensitization studies [ 28 , 29 ]. Two hours after the final injection, total RNA was prepared from the olfactory bulbs, midbrain and adrenal glands, all of which contain catecholaminergic neurons that express Th .…”

“…This porphyrin molecule stabilizes both G-quadruplexes and i-motifs, whereas its structural isomer, TMPyP2 ( Fig 1 ), does not [ 15 – 17 ]. Many studies using cultured cells have demonstrated that TMPyP4 can reduce cell proliferation and stabilize nucleic acid secondary structure to modify gene transcription levels [ 18 – 24 ], but only a handful have studied this compound in vivo [ 23 , 25 – 29 ]. These in vivo studies have primarily focused on the ability of TMPyP4 to reduce the size of tumors either by itself or in combination with photodynamic therapy rather than demonstrating that TMPyP4 can alter either gene transcription or translation levels in vivo .…”