Antitumor and Antimetastatic Effects of Toxoplasma Gondii in Mice with Lewis Lung Carcinoma

Lewis 폐암 마우스 모델에서 톡소포자충에 의한 항암 및 항전이 효과

Background : Immunotherapy is another treatment modality for various cancers. There is little information on the antitumor effects of immunotherapy on implanted lung cancer mouse models. Toxoplasma gondii is able to potently induce a nonspecific stimulation of the host immune system. Therefore, this study evaluated the antitumor and antimetastatic effect of nonspecific immune stimulation by T. gondii in a Lewis lung cancer mouse model. Methods : Female C57BL/6 mice were injected with either Lewis lung cancer cells ($1{\times}10^6$ per mouse) or 5 cysts from the T. gondii Me49 strain with various schedules. The number of survival days, the tumor size of the implanted muscle and the histopathological findings of each group were noted. In addition to these mice, the Toxoplasma antigen($50{\mu}g$ per mouse) or a lymphokine (0.5 ml per mouse) was added to boost the immunotherapy. Results : No mouse in the Toxoplasma-infected group had died, whereas the mice receiving only the cancer cells (cancer control) survived for $29.1{\pm}4.4$ days. Cancer cells were revealed from 1 week after cancer cell inceulation in the muscle and from 3 weeks in the lung of the cancer control, whereas cancer cells were found in both the preinfection control and coinfection control groups from 2 weeks and 4 weeks in the lung respectively. The in the number of survival days were $32.4{\pm}3.3$ in the mice receiving T. gondii 2 weeks prior to the cancer cells inoculation (preinfection control), $30.9{\pm}5.1$ in mice received both simultaneously (coinfection control), and $34.9{\pm}2.9$ in mice received T. gondii 2 weeks after cancer cells implantation (postinfection control). These 3 infection groups had significantly longer survival days and suppressed tumor growth than those of the cancer control. In addition to these mice, and injection with the Toxoplasma antigen alone or in combination with lymphokine resulted in a significant increase in the number of survival days. Conclusion : These findings suggest that an injection with T. gondii can induce the antitumor and antimetastatic effects in Lewis lung cancer mouse models. Moreover, these effects were increased with an injection of the Toxoplasma antigen alone or in combination with lymphokine. However, this therapy can not prevent the development of cancer.

배 경: 종양은 우리나라뿐만 아니라 선전 국가에서도 주요 사망 원인의 하나로, 새로운 치료법의 개발이 절실히 요구된다. 최근 면역종양학의 발전으로 면역강화요법에 의한 종양의 면역치료에 대한 관심이 높아지고 있다. 이에 본 연구는 Lewis 폐암 마우스 모델을 대상으로 원충의 일종인 톡소포자충 (Toxoplasma gondii)에 의한 비특이적 면역증강요법에 의한 폐암의 성장 및 전이 억제 효과를 평가하고자 시행하였다. 방 법: C57BL/6 마우스 톡소포자충 충체 (마우스당 5개의 씨스트를 복강내로 주사) 혹은 Lewis폐암세포 (마우스당 $1{\times}10^6$씩 대퇴근육에 주사)를 여러 조합으로 처치하여 각 군별 생존기간, 주사부위 근육의 종양크기, 근육 및 폐장의 조직병리 소견을 조사하였다. 또한 각 군별 마우스를 톡소포자충 항원(마우스당 $50{\mu}g$)혹은 lymphokine(마우스당 0.5ml)으로 추가 면역한 다음 항암 및 항전이 효과를 비교하였다. 결 과: 톡소포자충 충제만을 감염시킨 마우스는 실험기간중 한 마리도 죽지 않았으나, 폐암세포만을 주입한 마우스(폐암대조군)의 평균 생존기간은 $29.1{\pm}4.4$일이었다. 톡소포자충 감염 후 2주에 폐암세포를 주입한 마우스 (전감염대조군), 충체와 폐암세포를 동시에 주입한 마우스 (동시감염대조군) 및 폐암세포 주입 후 충체를 감염시킨 마우스(후감염대조군)의 생존기간은 각각 $32.4{\pm}3.3$일 $30.9{\pm}5.0$일 및 $34.9{\pm}2.9$일로 폐암대조군에 비하여 모두 유의하게 증가하였으며(0.0001