Novel therapeutic regimens for urethane‐induced early lung cancer in rats: Combined cisplatin nanoparticles with vitamin‐D₃

Abstract

Lung cancer remains incurable; therefore, novel therapeutical approaches are of great demand. This study was designed to investigate the effectiveness of cisplatin nanoparticles combined with vitamin-D 3 on urethane-induced early lung cancer in rats and to clarify the underlying signaling mechanisms. Early lung cancer was induced in male Wistar rats by urethane. Rats were divided into six groups: I-control, II-cancer untreated, III-cancer + free cisplatin, IV-cancer + cisplatin nanoparticles, V-cancer + free cisplatin + vitamin-D 3 , VI-cancer + cisplatin nanoparticles + vitamin-D 3. Inflammation, proliferation, and apoptosis were evaluated together with the levels of tumor marker CK-19 along with histological assessment. Treatment of lung cancer with either free or nanoparticles of cisplatin alone demonstrated significant suppression in the expression of inflammatory, anti-apoptotic and tumor markers compared to rats with lung cancer. Moreover, vitamin-D 3 supplementation with either cisplatin forms lead to a further decrease of all markers, markedly with cisplatin nanoparticles. The present study shows the synergistic effect of cisplatin-nanoparticles combined with vitamin-D 3 as a new therapy regimen against lung cancer. Further studies with larger sample sizes and longer duration are needed to confirm these results.

Anti-Cancer Role of Cassia alata Leaf Extract in a Rat Model of Lung Cancer

“…Our lung cancer model was similar to that of Radwan et al [36], who used four intra-peritoneal injections of EC at a dosage of 0.375 g/kg over 12 weeks with a 3-week gap between treatments to cause lung adenocarcinoma in rats. After twenty weeks of EC administration, Janker et al [22] found that three times of EC injections (1 mg/gm) a week significantly increased the number of tumor nodules in mice compared to a single injection, even though there was no death or morbidity and a 100% tumor incidence rate.…”

Relevance of Carcinogen-Induced Preclinical Cancer Models

“…Urethane is usually administered intraperitoneally or intravenously at doses ranging from 0.5 to 2 g/kg and can induce tumors within 6 to 12 months. Urethane-induced liver tumors are highly heterogeneous and can be classified into different histological subtypes, such as trabecular, pseudoglandular, and scirrhous [ 54 ].…”

Changes in the Cellular Composition of the Rat Thymus 90 Days After Urethane Injection Against the Background of Selenium Intake

“…Объектом исследования служил тимус. Количество животных, указанное в опытных группах, соответствует числу крыс, у которых через 90 дней после однократного введения уретана были обнаружены изменения в ткани легких в виде дисплазии альвеолярного эпителия, верифицированные классическими общегистологическими методами исследования [25].…”

“…Уретан-индуцированный канцерогенез участвует в развитии как доброкачественных, так и злокачественных опухолей, главным образом опухолей легких, и считается ценной экспериментальной моделью аденокарциномы человека. При внутрибрюшинном введении уретана крысам индуцируется развитие аденомы легких [25]. Уретан превращается ферментом CYP2E1 цитохрома Р450 в винилкарбамат, что приводит к образованию эпоксида (винилкарбаматный эпоксид), который ковалентно связывается с ДНК и может привести к неправильному включению оснований во время репликации ДНК, что приводит к точечным мутациям [17,19].…”